Introduction to Causes, Symptoms, and Treatments of Immunoglobulin A Deficiency

The most prevalent primary immunodeficiency is immunoglobulin A (IgA) deficiency, characterized by the presence of a low level of IgA in the bloodstream.  This disorder increases the possibility of mucous membrane infections in the ears, lungs, sinuses, as well as gastrointestinal tract.

People who suffer IgA deficiency are more likely to develop some immunodeficiency diseases. And studies have shown the functions of IgA for allergic diseases, autoimmune disorders, gastrointestinal (GI) diseases, etc.

What Is IgA?

IgA is the most common immunoglobulin in mucosal tissue in humans, with secretory IgA airway secretions accounting for around half of all IgA airway secretions. IgA is also the second most abundant protein in circulation, with roughly 90% of it occurring in monomeric form. Secretory IgA is often generated first, with systemic antibodies appearing later in the immune reaction. IgA in mucosal tissue has the ability to translocate across epithelial tissue, and to kill viruses intracellularly.

For example, IgA antibodies are found to be able to dominate the early SARS-CoV-2-specific antibody response in the serum, saliva, and bronchoalveolar lavage fluid of SARS-CoV-2-infected patients. This finding makes it possible to use IgA detection as an early diagnosis marker for detecting COVID-19.

What Is IgA Deficiency?

It's worth noting that IgA levels that are somewhat low are not indicative of IgA deficiency. Low IgA levels often indicate a weaker immune system. Poor sleep, allergies, digestive issues, chronic stress, certain medicines are all possible reasons.

A person with IgA deficiency must have a total absence or extremely low levels of IgA in their blood, at the same time with normal IgG and IgM levels.

What causes IgA deficiency?

IgA deficiency is a health condition that affects approximately one out of every five people. This indicates that it is a hereditary condition. It can, in rare situations, also be caused by certain medicines.

What Are the Symptoms of IgA Deficiency?

It's unclear why some individuals suffer several complications as a result of IgA deficit while others have none. The majority of patients with IgA deficiency do not report an increased level in infections. Some patients with IgA deficiency, although not all, are more susceptible to infections of the mucous membranes.

Sinusitis, lung infections, middle ear infections (otitis media), and GI tract infections, such as Giardiasis, are all possible side effects.

IgA deficiency has also been linked to a higher incidence of comorbidities. Various autoimmune disorders, such as certain blood diseases, systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease, are among them. Approximately 20-30% of patients with IgA deficiency develop these disorders.

What Is the Treatment for IgA Deficiency?

The most common therapy for IgA deficiency is to treat infections or any related disorders that may arise. If one has IgA deficiency and recurring infections, he or she should be treated as soon as possible. This can involve antibiotics for bacterial infections.

Vaccinations against common illnesses, such as the seasonal influenza vaccination and the pneumococcal vaccine, are also suggested. 

Novel Research on Broad Spectrum Neutralizing Antibodiesfor HIV Treatment

AIDS is an extremely dangerous infectious disease caused by HIV, a virus that takes the most important CD4T lymphocytes in the human immune system as its main target and destroys a large number of these cells, causing the body to lose its immune function. Therefore, AIDS patients are susceptible to various diseases and can develop malignant tumors and have a high death rate.

In the long journey of fighting against AIDS, scientists have not stopped exploring. As there is no effective vaccine on market yet, patients have to take antiviral drugs for life, and there are many problems such as poor adherence and drug resistance.

In recent years, a variety of new anti-HIV therapies have emerged, among which broad-spectrum neutralizing antibodies, as one of the most cutting-edge hotspots, are expected to play an important role in the functional cure or even the eradication of AIDS, bringing a disruptive breakthrough.

It is well known that HIV is a very cunning adversary that changes very quickly, and whenever it encounters an attack by the human immune system, it quickly changes to escape from the hunt, which is very conducive to its long-term survival and continuous transmission in the host.

In the process of the fighting between the human body and the virus, a special anti-HIV component, broad-spectrum neutralizing antibodies, has been produced, which can recognize the areas on the surface of the HIV strain that are not easily changed, thus having the ability to capture multiple strains, inhibit the replication of the virus in the patient's body, and effectively reduce the level of HIV in the human body.

However, it is very difficult to produce this type of HIV killer in naturally infected people, and only 10-15% of people infected with HIV can produce neutralizing antibodies, of which only 2%-5% have broad-spectrum neutralizing antibodies, i.e., they can neutralize more than 80% of HIV strains prevalent worldwide.

Studies have shown that the production of broad-spectrum neutralizing antibodies may be related to factors such as viral load, viral diversity, and duration of infection.

With deepening interdisciplinary collaboration and great progress in the field of technology, scientists can successfully isolate purified antibodies with broad-spectrum neutralizing activity from the blood of infected patients and actively promote anti-HIV research. Broad-spectrum neutralizing antibodies can kill the virus not only by directly neutralizing the virus strain, but also by stimulating other immune components in the body to work together to kill the virus, achieving the dual purpose of boosting immunity and killing the virus.

On February 2, 2022, researchers at the Institute Pasteur in France published a paper in Nature Communications on the mechanism of HIV neutralizing antibodies as a therapeutic tool. This study used immunofluorescence techniques and electron microscopy to analyze the CD4bs of HIV neutralizing antibodies, V1/2 and V3 epitopes antibodies that form immune complexes with viral particles on the surface of infected cells in aggregates.

This study determined the antiviral activity of neutralizing antibodies in addition to their neutralizing and Fc effects, i.e., they impede HIV release by binding viral particles to the surface of infected cells.

Due to the current impressive performance of HIV broad-spectrum neutralizing antibodies in animal and clinical trials, an increasing number of antibodies have been explored in trials for clinical treatment. In addition, for AIDS diagnosis, research also found that HIV infection appears to alter natural antibody levels in ways that may increase the risk of atherosclerosis and may impact the pathogenesis of rheumatic heart disease (RHD), indicating different autoantibodies self-components may be used as early biomarkers for AIDS detection.

Scientists are still working on the exploration of antibodies covering both neutralizing antibody for AIDS treatment and natural autoantibody for AIDS diagnosis, and it’s believed that these strategies will pave the way for a universal cure of HIV and significantly reduce the number of people who today still struggle with the disease.

Rabies and Rabies Vaccine: What You Should Know

Rabies is an acute infectious disease caused by the rabies virus that attacks the central nervous system of humans and animals, and is listed as the world's most deadly infectious disease by World Health Organization (WHO).

The initial symptoms of rabies are fever, fatigue, restlessness, nausea, followed by a period of euphoria and a state of high excitement, with an expression of extreme terror, irritability, and a sense of impending death, and finally a period of coma, which lasts only 6-18 hours.

However, the public often has some misconceptions about rabies, and this article will list the common misconceptions.

Misconception 1: Healthy dogs carry the virus too.

The findings of studies by Centers for Disease Control and Prevention (CDC) deny this statement that healthy dogs transmit rabies virus.

Misconception 2: The incubation period of the virus lasts for dozens of years.

The World Health Organization has proven through very detailed viral genome studies that the incubation period of rabies virus is generally 2 weeks-3 months, and 99% of patients infected will develop symptoms within a year, and it is rare to take more than a year, with a maximum incubation period of only 6 years.

Misconception 3: One must be vaccinated within 24 hours of being bitten by a dog.

Vaccination is not always necessary after a dog bite. The World Health Organization (WHO) gives a 10-day observation method.

After the wound is disinfected, it is best to observe the biting animal. If the dog or cat does not die within 10 days after the bite, and there are no symptoms of rabid dog or cat, it can prove that the biting animal does not contain rabies virus in its saliva at the time of the incident, and vaccination is not necessary. In the case of other animals that cannot be observed in captivity, please get rabies vaccination immediately.

In addition, according to the WHO regulations, the principle of rabies vaccination is that the earlier the vaccination, the better the effect, preferably within 24 hours. If the vaccine is given more than 24 hours later, the vaccine can be effective as long as the person has not yet developed the disease before the vaccine stimulates the body to produce sufficient immune antibodies.

Misconception 4: Vaccination is required for dog licking wounds.

In a report released by the CDC in 2008, the probability of rabies transmission was evaluated for eight situations in which dog bites, cats licking wounds, dogs licking wounds, and contact with rabies patients in hospitals are related to a pathopoiesis rate of1 in 100,000, which means that vaccination is generally not necessary in these situations.

Misconception 5: Another vaccination is necessary if one is bitten again.

The experts at the Queen Saewabha Memorial Research Institute in Thailand, a WHO Collaborating Center for Rabies Pathogenesis and Prevention Research, have responded to the question of vaccine use by saying that only three doses of vaccine (on the first day of the bite, on the third day, and on the seventh day) are sufficient for future prevention, and that there is no need to inject immune serum when bitten by a rabid animal again in the future; and that if the dog that bites a human remains healthy after 10 days of observation, the vaccine treatment of the patient should stop.

Rabies is the most severe acute viral infection of humans, but no effective therapies have been identified to rescue a patient who has developed symptoms. The past decade has seen intense interest in the treatment of rabies, and treatments such as antibody and peptide discovery targeting rabies virus have been proved to cure rabies in preliminary animal studies, even after they showed symptoms of rabies in their brains. If the following research shows the same results in humans, it would be a breakthrough for treating people with rabies infection even after it reaches the brain.

Two Faces of Adenovirus - A Time to Kill, A Time to Heal

Viruses are a kind of non-cellular organisms that are tiny to the nanometer level, with a simple structure that only has a protein shell and a long nucleic acid chain as genetic material. It cannot be independently metabolized but must be parasitic in living cells and multiply in a replication mode. It is weak but also strong, and human beings have to face the two-sided nature of a kind.

Adenovirus is such a virus that can infect human body. They are widespread in nature and can cause infections of the respiratory tract, eyes, gastrointestinal tract, and urinary system. They can cause regional transmission in highly confined, crowded and humid environments. But the advancement of science and technology helps us discover that this type of virus can also be used to fight tumors and even the novel coronavirus disease, COVID-19, that has recently raged around the world.

· Adenovirus Infection Can Be Dangerous

Adenovirus infection will cause many uncomfortable symptoms, including symptoms of upper respiratory tract infection (fever, sore throat, nasal congestion and other common cold symptoms), conjunctivitis (such as pharyngeal conjunctivitis, conjunctivitis, epidemic keratoconjunctivitis), gastrointestinal infection (diarrhea, more common in children under 5 years old), urinary tract infections, hemorrhagic cystitis, etc.

Adenovirus infection is a contagious disease and should be actively prevented. Adenovirus transmission mainly includes contact transmissions of respiratory droplets, pollutants and excrement, and eye secretions.

· Adenovirus Help Fight Tumors

Oncolytic viruses are currently an important method in the field of tumor immunotherapy. At present, Adenoviruses are the most used type in clinical trials. Oncolytic adenovirus is a genetically engineered adenovirus that can selectively replicate and express in tumor cells, thereby lysing tumor cells.

In 1996, since the world's first oncolytic adenovirus ONXY-015 was launched in clinical research, it has been widely used in scientific research, involving a variety of solid tumors. Oncolytic adenovirus combined with radiotherapy, chemotherapy, and targeted drug therapy are also proved to be more effective treatment options. Further clinical research will continue to explore the potential of oncolytic virus combined with other therapies.

· Adenovirus Vaccine for SARS-CoV-2

Adenovirus-vectored COVID-19 vaccines are one of the hot topics in global news. Johnson & Johnson’s JNJ-78436735, CanSino Biologics’ Convidicea (AD5-nCoV) and Russia’s Sputnik V, AZD1222 are all examples of this type. So what kind of vaccine is it? How does it work?

Like all vaccines, this method is designed to trick our body into getting infected. These homemade spike proteins will train our bodies to detect and terminate any actual SARS-CoV-2 infection before the virus causes severe damage. The adenovirus vector COVID-19 vaccine constructs the gene of S protein of SARS-CoV-2 into the adenovirus genome, and the shell is still the normal shell protein of the adenovirus. Therefore, when adenovirus infects host cells, the genes encoding the SARS-CoV-2 S protein are released to the host cell, and S protein is synthesized in the cytoplasm, which stimulates a series of immune responses.

The advantage of an adenovirus-based vaccine is that it can induce humoral and cellular immunity at the same time. Humoral immunity produces antibodies that bind to viruses, preventing viruses from entering human cells, that’s to say, viruses are recognized, swallowed, and degraded by macrophages outside the cells. For viruses that have been lucky enough to enter cells, they can be recognized by cellular immune mechanisms and cytokine secreted by killer T cells to lyse the infected cells.

CAR-T Therapy as Reborn Chimera to Cure Cancers

In Greek mythology, the Chimera was a fire-breathing she-monster with a lion's head, a goat's body, and a dragon's tail. And nowadays, chimera has been reborn as a healer instead of a killer—chimeric antigen receptor T cell (CAR-T) therapy is saving lives suffering from hard-to-treat cancer.

Antibodies can bind to proteins and recognize foreigners through the spatial structure of the protein on the surface of cancer cells. It has a powerful and efficient capability on recognition, but is not able to kill cancer cells. While T cells have a powerful killing function, however, cancer cells that survive natural selection can "deceive" T cells and avoid being recognized by them. So, wouldn’t it be a perfect plan if the recognition function of antibodies be combined with the killing function of T cells?

CAT-T therapy is such a chimera, which combines antibodies and T cells together. As one of the skeleton staffs in the department of immunotherapy, CAR-T therapy has undergone four great improvements and has made great progress in the treatment of leukocytes and other hematological malignancies.

The First Generation of CAR Technology

The structure of the intracellular segment of the first generation of CAR-T cells is relatively simple, mainly composed of the immunoreceptor tyrosine-based activation motif (ITAM) of the CD3 molecule ζ chain. And it lacks the second signal necessary for T cell activation, that is, the costimulatory signal. Therefore, the first-generation CAR-T cell must interact with costimulatory molecule ligands on the surface of the antigen-presenting cells, thereby obtaining natural costimulatory signals, which makes it less efficient in activation, obtaining very limited curative effect in clinical applications.

The Second Generation of CAR Technology

On the basis of the first generation, the second generation of CAR-T cells adds an ITAM from the costimulatory molecule CD28 or CD137 to the intracellular segment, and after the binding of the extracellular antigen recognition region and target antigen, T cells can obtain antibody stimulation signals and costimulatory signals at the same time. This makes the activation ability of the second generation far stronger than the first, which shows surprising therapeutic effects in clinical treatment. But here is another problem—the activation signal transmitted by CD28 is stronger, which enables T cells to achieve a high killing activity in a shorter period of time; while the activation signal transmitted by CD137 maintains for a longer period of time. Since the second-generation CAR-T cells mostly used retroviruses as vectors, and the gene fragments that can be accommodated and carried are limited, it is difficult to simultaneously transfect the ITAMs of both CD28 and CD137 into T cells. Therefore, researchers have to choose between a stronger activation intensity and longer activation persistence.

The Third Generation of CAR Technology

The third-generation CAR-T cells use lentivirus as a transfection vector, which can carry larger gene fragments into T cells, that’s to say, the intracellular segment can often contain 2 or more ITAMs. However, some studies have shown that the killing activity of the third-generation CAR-T cells has not been significantly improved. This may be because the activation signal generated by an ITAM of a costimulatory molecule in the T cells has already reached the threshold, so simply adding ITAM area in quantity will not further enhance the activation effect of CAR-T cells.

The Fourth Generation of CAR Technology

The fourth-generation CAR-T cells are known for their precision. The design of this generation is mainly considered from the perspective of precise treatment of tumors and other diseases. Another improvement is to control the survival time of CAR-T cells, which usually can survive in patients for more than 10 years and may attack normal cells by recognizing tumor-associated antigens on their surface. Therefore, some researchers have added controllable suicide genes to the structure of CAR, so as to control the survival time of CAR-T cells in human body. What’s more, CAR-T cells were mainly used for the treatment of hematological tumors, and no significant results have been seen in the treatment of solid tumors. This is mainly because CAR-T cells often cannot enter the tumor. Some researchers have added the receptor structure of cytokines or chemokines to the CAR design, thereby increasing the infiltration of T cells in tumor tissues, achieving the effect of enhancing the killing of solid tumors.

CAR-T therapy has been proved to be a potential treatment for tumors and has been a hot topic among global researches. Aiming at accelerating the process of drug or therapy development, Creative Biolabs offers custom service covering the entire CAR-T therapy development steps to best suit any technical, program and budget requirements.

 CRISPR Gene-Editing Pushes Forward Therapy for Novel Treatment forChronic Pain

Recently, studies have proved that CRISPR-based gene silencing technology can alleviate chronic pain in mice. Although the therapy is still a long way from human use, scientists predict that it is a promising way to eliminate chronic pain that lasts for months or years.

In 2018, the World Health Organization (WHO) included chronic pain as an independent disease in its classification catalog for the first time. Chronic pain refers to pain that lasts or recurs for more than 3 months. The occurrence and development of chronic pain involve biological, psychological and social factors, since it can cause serious consequences such as sleep disturbance, lack of appetite, mental breakdown and even personality distortion and home violence. Many patients commit suicide because they cannot tolerate this long-term pain. Chronic pain is usually treated with opioids (such as morphine), which can lead to addiction, and thus the state has strictly controlled the use of such drugs, which further reduces the scope of patients' choices.

This dilemma inspired Ana Moreno and his colleagues at the University of California, San Diego to actively seek alternative treatments—CRISPR-based gene silencing technology.

Traditional CRISPR technology is to edit a person's genome as a treatment for blood diseases and certain genetic blindness. CRISPR, which treats chronic pain, does not directly edit genes, but it prevents gene expression, so it will not cause permanent changes.

When a stimulus triggers a neuron to send an electrical signal through a nerve in the spinal cord and upload it to the brain, pain will appear in the brain. When ion channels on a neuron open or close to allow ions to pass through, the ions conduct electrical current along the nerve. For chronic pain, part of this pathway becomes abnormally active. Although there are many types of ion channels, studies have shown that a sodium channel called Nav1.7 may play an important role in chronic pain. When the genetic code of this channel is mutated, people either experience extreme, constant pain, or feel no pain at all.

So Moreno and her team believe that preventing neurons from producing Nav1.7 can prevent pain signals from being transmitted to the brain. The team developed gene silencing therapy using CRISPR/Cas9, which won the Nobel Prize last year, and conducted experiments on mice. After implementing gene silencing therapy, they injected chemotherapy drugs or inflammatory agents to induce chronic pain. The results showed that these mice are more tolerant of painful stimuli. The results of the study were published on Science Translational Medicine on March 10, 2021.

In some cases in the experiment, pain relief can last up to 44 weeks after injection. More importantly, this therapy seems to reduce the expression of Nav1.7 without closing other sodium channels, and the mice did not lose any sensation other than pain, nor did they exhibit any side effects.

Although these preliminary results give people hope, it is not yet certain whether there will be the same pain relief effect in humans.

After 30 years of setbacks, gene therapy is currently developing rapidly and has become a key component of the treatment of various genetic and acquired diseases in humans. Gene therapy of inherited immune system diseases, hemophilia, eye and neurodegenerative diseases has brought great hope to mankind. Scientists and clinicians are engaged in basic, translational, and clinical research. With the support of the government and charity organizations, innovative or improved technologies will continue to emerge. Mankind can remain optimistic that gene therapy will become an important treatment for serious human diseases.

CAR-T Cell Therapy & Surgery for Solid Tumor Treatment: The Whole is Greater Than Sum of Parts

The past decade has witnessed ongoing progress in immune therapy to ameliorate human health. As an emerging technique, chimeric antigen receptor (CAR) T-cell therapy has the advantages of specific killing of cancer cells, a high remission rate of cancer-induced symptoms, rapid tumor eradication, and long-lasting tumor immunity, opening a new window for tumor treatment.

CAR T cell therapy works by reprogramming patients' own immune cells to attack their tumor cells. A recent study conducted by researchers in the Perelman School of Medicine at the University of Pennsylvania found that this therapy may also enhance the effectiveness of surgery for solid tumors.

The study is published in Science Advances on Jan. 11, 2023, titled “Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma”, and reports that the research found a method to allow the mice to survive the tumor recurrence.

Surgery is highly effective if the solid tumor has not spread. The main obstacle is that during the surgery, it’s usually hard for surgeons to clearly distinguish a tumor from the surrounding healthy tissues. Thus, post-surgical recurrence due to remaining microscopic tumor cells is common.

The research team tried to find an answer to this obstacle with an eye to applying an anti-tumor treatment to kill any residual tumor cells immediately after tumor removal, and they tested with CAR T cells for two cancer types: triple-negative breast cancer (TNBC), which lacks all of the three major breast cancer markers, and pancreatic ductal adenocarcinoma (PDA), the most common type of pancreatic cancer. Both types are notoriously hard to cure.

The CAR T cells were engineered to home in on the protein mesothelin, a surface marker on both types of tumor cell in the experiments. Without the CAR T cell and fibrin gel, the remaining tumor tissue grew and the mice succumbed within about seven weeks. With the gel, however, residual tumor tissue swiftly disappeared in 19 of 20 mice, and these animals survived without wound-healing complications or other apparent side effects for the remainder of the observation period.

Further experiments showed that CAR T cells targeting mesothelin have the potential to attack healthy cells bearing that protein marker after intravenous injection, and the toxicity was decreased by local injection of the CAR T cells compared to direct injection of the cells into the blood.

“This study demonstrates the promise of CAR T as an add-on to surgery for solid tumors. And this approach can be broadened to deliver other cellular therapies and anticancer agents in addition to CAR T cells, potentially boosting the antitumor effectiveness even further.” commented a scientist at Creative Biolabs, a biotech company providing TCR and CAR T therapy development services as well as ready-to-use TCR and CAR T&NK cell construction products.

Researchers all over the world are trying to enhance the effectiveness and safety of CAR T-cell therapy, and it’s believed that this direction will be a big step toward curing cancer.

AI for Pharma: First Antibody Drug Designed Using AI Is Writing A New Chapter

Artificial intelligence (AI) technology has beaten humans at games of chess and become famous globally. Now, AI and machine learning (ML) have revolutionized almost all types of industries. In a data-driven age where companies across all parallels of the industry are adopting big data and AI technologies, the pharmaceutical industry is no exception.

Bimekizumab is the first-in-class monoclonal antibody, which has been approved for the treatment of plaque psoriasis in Europe and is in clinical trials for other indications including psoriatic arthritis and ankylosing spondylitis. What makes Bimekizumab unique is that it is the computational design that generated the exact final drug candidate.

Unlike the other bispecific antibodies that aim at two targets specifically with two arms, Bimekizumab has two identical arms and each arm hits both targets, which are IL-17A and IL-17F targets. If one arm is swapped to hit another target, the antibody can potentially cover three targets, which may contribute to the decreased immunogenicity risk and manufacturing cost. In addition, it may also be further modified into an antibody-drug conjugate.

That’s to say the possibilities are vast as the drug can be used as a platform for further drug discovery and development.

This first AI-assisted drug is actually writing a new chapter for his whole industry. Areas impacted include improved decision-making, reduced manual groundwork, and the upgraded pharma and healthcare systems across many areas in the healthcare sector, covering: 

R&D

Pharma companies around the world are leveraging advanced ML algorithms and AI-powered tools to streamline the drug discovery process. For example, Creative Biolabs, a biotech company, has launched the AI-based Antibody Discovery Platform combining AI, ML, and big data, which can generate 10 times more antibody sequence clusters than a laboratory-based approach alone.

Disease Diagnosis

Machine Learning systems can be established to collect, process, and analyze vast volumes of patients’ healthcare data, and ML technologies can help quicken the diagnosis process, thereby helping save millions of lives.

Epidemic Prediction

AI and ML are already used by many healthcare organizations to monitor and forecast epidemic outbreaks across the globe, which can disparate sources on the web, and study the connection of various geological, environmental, and biological factors on the health of the population of different geographical locations.

Remote Monitoring

Remote monitoring is a breakthrough in the pharma and healthcare sectors. Many pharma companies have already developed wearable patient monitoring devices powered by AI algorithms that can remotely monitor patients suffering from life-threatening diseases.

Manufacturing

AI in the manufacturing process can be outstanding by higher productivity with improved efficiency. AI can be used to manage and improve all aspects of the manufacturing process, including quality control, predictive maintenance, waste reduction, design optimization, and process automation.

Currently, AI has been a chic catchphrase in health care. Its application is starting to have a significant impact on automation technologies used across the pharma industry. It has the potential to transform drug discovery and does what humans do, but more efficiently, more quickly, and at a lower cost.

Current And Future Research Directions of Stem Cells

In recent years, research related to stem cells has created a boom in the biomedical field. Stem cells, with their advantages of easy access, low immunogenicity, and no ethical controversies, have successfully stood out in the era of cell therapy and become one of the key research directions nowadays. The development of technologies such as gene editing and stem cells surface engineering has greatly contributed to the optimization of stem cell therapy.

Up to now, several research results worldwide have confirmed that stem cell technology has immeasurable value in multiple applications such as human disease treatment, tissue engineering, and even anti-aging cosmetic industry.

Stem Cells for Disease Intervention

Among the stem cell-related research, the most anticipated one is the stem cell therapy with stem cells as the core. It operates by replacing diseased or cancerous cells in the patient's body with normal functional stem cells as the donor to achieve effective intervention in human diseases

So far, stem cell therapy has achieved great success in many clinical trials worldwide. Up to now, several clinical studies have confirmed that stem cells can effectively intervene in more than 140 diseases, including autoimmune diseases, inflammatory diseases, neurodegenerative diseases, motor neuron diseases, respiratory diseases, metabolic diseases, and cardiovascular and cerebrovascular diseases.

Stem Cells for Organ Regeneration

Stem cells have multi-directional differentiation potential, and under specific conditions, through induction, they can differentiate and regenerate into neural stem cells, liver cells, pancreatic islet cells, cardiomyocytes, and so on. This property provides a new idea for tissue engineering. The regeneration of tissues and organs using stem cells has become an important direction in tissue engineering research.

And in the past two years, many remarkable results have emerged in the regenerative medicine community. For example, in June 2021, scientists successfully cultured skin organoids using human pluripotent stem cells, forming multiple layers of skin tissue, even containing hair follicles, sebaceous glands and neural circuits, which are expected to possess the complexity and function of natural skin.

Stem Cells for Anti-aging Cosmetics

Research shows that the aging of human body is closely related to the decrease of adult stem cells. Stem cell-related anti-aging technology is a new technology to replenish the body with adult stem cells.

It is based on the mechanism of providing the body with exogenous stem cells with high vitality, allowing these cells to perform the functions of cell renewal, tissue repair and immune regulation in the body, and finally achieving anti-aging effect. In addition, studies have shown that stem cells can activate the function of epidermal cells, thus restoring skin firmness and elasticity.

It’s now been 16 years since the ability to generate iPS cells (induced pluripotent stem cells) was hailed as a game changer for regenerative medicine. Even with the challenges remaining, stem cell therapy is becoming a more tangible reality by the day. Stem cells, as the main force of the era of cell therapy, will bring disruptive changes to the field of human health and play a huge role in many research fields.

Current State and Future Trends of Stem Cell Therapy Research

In recent years, research related to stem cells has created a boom in the biomedical field. Stem cells, with their advantages of easy access, low immunogenicity, and no ethical controversies, have successfully stood out in the era of cell therapy and become one of the key research directions nowadays. The development of technologies such as gene editing and stem cells surface engineering has greatly contributed to the optimization of stem cell therapy.

Up to now, several research results worldwide have confirmed that stem cell technology has immeasurable value in multiple applications such as human disease treatment, tissue engineering, and even anti-aging cosmetic industry.

Stem Cells for Disease Intervention

Among the stem cell-related research, the most anticipated one is the stem cell therapy with stem cells as the core. It operates by replacing diseased or cancerous cells in the patient's body with normal functional stem cells as the donor to achieve effective intervention in human diseases

So far, stem cell therapy has achieved great success in many clinical trials worldwide. Up to now, several clinical studies have confirmed that stem cells can effectively intervene in more than 140 diseases, including autoimmune diseases, inflammatory diseases, neurodegenerative diseases, motor neuron diseases, respiratory diseases, metabolic diseases, and cardiovascular and cerebrovascular diseases.

Stem Cells for Organ Regeneration

Stem cells have multi-directional differentiation potential, and under specific conditions, through induction, they can differentiate and regenerate into neural stem cells, liver cells, pancreatic islet cells, cardiomyocytes, and so on. This property provides a new idea for tissue engineering. The regeneration of tissues and organs using stem cells has become an important direction in tissue engineering research.

And in the past two years, many remarkable results have emerged in the regenerative medicine community. For example, in June 2021, scientists successfully cultured skin organoids using human pluripotent stem cells, forming multiple layers of skin tissue, even containing hair follicles, sebaceous glands and neural circuits, which are expected to possess the complexity and function of natural skin.

Stem Cells for Anti-aging Cosmetics

Research shows that the aging of human body is closely related to the decrease of adult stem cells. Stem cell-related anti-aging technology is a new technology to replenish the body with adult stem cells.

It is based on the mechanism of providing the body with exogenous stem cells with high vitality, allowing these cells to perform the functions of cell renewal, tissue repair and immune regulation in the body, and finally achieving anti-aging effect. In addition, studies have shown that stem cells can activate the function of epidermal cells, thus restoring skin firmness and elasticity.

It’s now been 16 years since the ability to generate iPS cells (induced pluripotent stem cells) was hailed as a game changer for regenerative medicine. Even with the challenges remaining, stem cell therapy is becoming a more tangible reality by the day. Stem cells, as the main force of the era of cell therapy, will bring disruptive changes to the field of human health and play a huge role in many research fields.

Escherichia Coli as a Model Organism and Its Application in Biotechnology

Model organisms are a group of organisms that can be used to study and reveal certain biological phenomena with universal patterns in living organisms. E. coli is one of the classic model organisms.

E.coli is not a rare organism, but present in all of us, and it is an important normal flora in our intestinal tract, providing us with vitamin K2, which we cannot synthesize ourselves. However, it can also be bad sometimes-when our immunity is weakened, it can become a pathogen, potentially causing infections outside our intestinal tract, such as sepsis and urinary tract infections. On the other hand, there are some species of E. coli that are pathogenic and can cause gastroenteritis in humans, leading to abdominal pain, fever, diarrhea, etc.

In 1885, Theodor Escherich, a German-Austrian pediatrician, discovered the bacterium in the feces of healthy people, and because it was found in the colon, it is named Escherichia coli. at first, E. coli was considered as a common intestinal bacterium, but later American scientists Stanley Norman Cohen and Herbert Boyer applied E. coli to genetic engineering.

Cohen was working on bacterial plasmids, and Boyer was interested in a restriction endonuclease in E. coli that recognized specific nucleotide sequences and thus cut the nucleotide chain down the middle. In 1973, they published a paper summarizing their results, which announced the dawn of genetic engineering.

In addition to genetic engineering, E. coli has an irreplaceable role as a model organism in the study of bacterial physiology and behavior. The most commonly used strain in the laboratory is the K12 strain of E. coli, which has lost its ability to survive in the intestine compared to the normal wild-type E. coli strain, but is well suited for laboratory studies and propagation in laboratory environments. Using E. coli K12, American scientists Joshua Lederberg and Edward Tatum have discovered the unique bacterial conjugation, which provides a very good method for scientists to conduct research on molecular biology and microbial genetics, such as the exchange of genetic material between different strains of bacteria.

Finally, E. coli is also emerging as a potential player in bioenergy. For example, Hiroyasu Yamamoto et al. successfully genetically modified E. coli in 2011 to convert sugar from plants into hydrocarbons almost identical to conventional diesel, which they call "biodiesel"; Pauli Kallio and his team, similarly genetically modified E. coli in 2014 to produce propane, a clean energy source with a large market need.

There are many more studies on E. coli, and no one expected that this little guy, which was originally only in our intestines, has now been deeply integrated into both medical research and daily life and industrial production.

Creative Biolabs has been working in anti-bacterial biomolecular discovery for decades, and has established the state-of-art Anti-Bacteria Biomolecular Discovery platform for E. coli. antibody discovery and peptide discovery. The experienced scientists utilize diverse technologies such as phage display, hybridoma technology, peptide array, etc., to provide reliable services to facilitate the anti-Escherichia projects for global customers.

What Is Immunoglobulin A Deficiency?

The most prevalent primary immunodeficiency is immunoglobulin A (IgA) deficiency, characterized by the presence of a low level of IgA in the bloodstream.  This disorder increases the possibility of mucous membrane infections in the ears, lungs, sinuses, as well as gastrointestinal tract.

People who suffer IgA deficiency are more likely to develop some immunodeficiency diseases. And studies have shown the functions of IgA for allergic diseases, autoimmune disorders, gastrointestinal (GI) diseases, etc.

What Is IgA?

IgA is the most common immunoglobulin in mucosal tissue in humans, with secretory IgA airway secretions accounting for around half of all IgA airway secretions. IgA is also the second most abundant protein in circulation, with roughly 90% of it occurring in monomeric form. Secretory IgA is often generated first, with systemic antibodies appearing later in the immune reaction. IgA in mucosal tissue has the ability to translocate across epithelial tissue, and to kill viruses intracellularly.

For example, IgA antibodies are found to be able to dominate the early SARS-CoV-2-specific antibody response in the serum, saliva, and bronchoalveolar lavage fluid of SARS-CoV-2-infected patients. This finding makes it possible to use IgA detection as an early diagnosis marker for detecting COVID-19.

What Is IgA Deficiency?

It's worth noting that IgA levels that are somewhat low are not indicative of IgA deficiency. Low IgA levels often indicate a weaker immune system. Poor sleep, allergies, digestive issues, chronic stress, certain medicines are all possible reasons.

A person with IgA deficiency must have a total absence or extremely low levels of IgA in their blood, at the same time with normal IgG and IgM levels.

What causes IgA deficiency?

IgA deficiency is a health condition that affects approximately one out of every five people. This indicates that it is a hereditary condition. It can, in rare situations, also be caused by certain medicines.

What Are the Symptoms of IgA Deficiency?

It's unclear why some individuals suffer several complications as a result of IgA deficit while others have none. The majority of patients with IgA deficiency do not report an increased level in infections. Some patients with IgA deficiency, although not all, are more susceptible to infections of the mucous membranes.

Sinusitis, lung infections, middle ear infections (otitis media), and GI tract infections, such as Giardiasis, are all possible side effects.

IgA deficiency has also been linked to a higher incidence of comorbidities. Various autoimmune disorders, such as certain blood diseases, systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease, are among them. Approximately 20-30% of patients with IgA deficiency develop these disorders.

What Is the Treatment for IgA Deficiency?

The most common therapy for IgA deficiency is to treat infections or any related disorders that may arise. If one has IgA deficiency and recurring infections, he or she should be treated as soon as possible. This can involve antibiotics for bacterial infections.

Vaccinations against common illnesses, such as the seasonal influenza vaccination and the pneumococcal vaccine, are also suggested. 

Creative Biolabs Unveils GTOnco™ Immuno-oncology Assay Services at Immuno-Oncology Summit

Immuno-oncology (IO), emerging as a novel approach to taking advantage of the body's immune system to fight cancer, has been a game changer in cancer treatment research. With abundant drug development experience over the past years, Creative Biolabs is dedicated to offering a full range of IO therapy development services, and recently has introduced upgraded GTOnco™ immuno-oncology assay services at the 10th Annual Immuno-Oncology Summit on October 12, 2022.

Creative Biolabs participates in this great event in the field of IO research as the corporate sponsor and exhibitor. The on-site scientists enjoyed the brilliant speeches, especially about new emerging technologies for IO targeting and discovery and overcoming resistance to IO therapy, and met many old and new friends on booth #9. The most asked service is the newly-updated immuno-oncology assay services, which cover:

GTOnco™ I-O Assays for In Vitro Study

For gene therapy-based I-O drug discovery, Creative Biolabs has updated a variety of proof-of-concept in vitro assays to test the pharmacological activity with a groundbreaking platform for in vitro testing of I-O agents.

The platform will greatly facilitate immune system activation study by well-established and custom designed assays, specifically for the research on cytokine release and activation of various immune cells. 

Immune cell-mediated anti-tumor effect study is another focus of Creative Biolabs’ scientist team, who is experienced in a variety of immune cell-mediated cancer cell killing strategies including NK or effector T cells. A range of in vitro assay services to study the regulation of the tumor microenvironment and immune cell-mediated anti-tumor immune response profiling are also available to support clients’ gene therapy-based I-O drug discovery.

GTOnco™ I-O Assays for In Vivo Study

This innovative platform also provides a comprehensive approach for in vivo efficacy studies and underlies the safety profile and action mechanisms of candidate I-O drugs, in the presence of a functionally immunocompetent system.

For in vivo cytokine response assay, Creative Biolabs provides various cytokine detection by ELISA or ELISpot assays, such as chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors.

For lymphocyte activation and proliferation assays, Creative Biolabs is able to provide faster, easier-to-use methods for measuring T-cell activation and proliferation in response to a variety of stimuli.

GTOnco™ also covers unique needs of clients’ projects by offering T cell persistence & trafficking assay, immune cell-mediated tumor regression assay, TCR-pMHC dissociation kinetics, and redirected T cell cytotoxicity assay

On December 4-8, 2022, Creative Biolabs will participate in the Antibody Engineering & Therapeutics (US) in San Diego, CA, and look forward to meeting more friends at booth #418. Find more information about one-stop gene therapy development services and upcoming events at https://www.creative-biolabs.com/gene-therapy/.

About Creative Biolabs

With years of experience in providing one-stop preclinical development services, Creative Biolabs has built a team of experts with solid knowledge of gene therapy, and is fully competent in providing services for worldwide clients. The services include but are not limited to gene delivery system development, gene editing, RNAi therapy development, safety and toxicology analysis, potency tests, and solutions of specific gene therapy development for diseases.

An Introduction to Major and Minor Histocompatibility Antigens

On the surface of healthy cells, there are special molecules called major histocompatibility complex (MHC). They play a key role in presenting foreign antigens to immune cells, especially by activating T cells. They work for the adaptive immune system. Major histocompatibility molecules are present in almost all nucleated healthy cells of humans. Mature red blood cells are the only type of human cells that do not have MHC molecules on the surface. Human leukocyte antigen (HLA) genes are the genes that code MHC molecules. Structurally, major histocompatibility antigens are transmembrane glycoproteins having portions that span the plasma membrane.

Generally, MHC molecules vary among individuals. There are two classes of MHC. They are class I MHC antigens and class II MHC antigens. Class I MHC molecules are found in all cells while class II MHC molecules are found only on the surface of antigen-presenting cells such as monocytes, macrophages, and dendritic cells, which are involved in immune reactions. Antigen presentation with MHC II is essential for the activation of T cells. MHC I antigens are essential for the presentation of normal “self” antigens.

While minor histocompatibility antigens (MiHAs) are small peptides found on cell surfaces. Therefore, MiHAs are short segments of proteins which are diverse. They are polymorphic in a given population. Structurally, they are composed of around 9 to 12 amino acid sequences. Generally, they are found associated with MHC antigens on the cell surface. These antigens can be either expressed ubiquitously in most tissues or expressed restrictively in immune cells. Predominantly, they are expressed on hematopoietic cells.

MiHAs are most found on the cellular surface of donated organs. In some organ transplants, they cause immunological responses. But they cause problems of rejection less frequently than MHC. However, even the donor and recipient are identical with regard to MHC genes; minor histocompatibility antigens can also mediate rejection due to amino acid differences. 

“Efforts to prevent graft-versus-host disease could be targeted through this pathway by matching for these MiHA or by preventing antigen recognition. Alternatively, these MiHA could be exploited as targets for a more potent graft-versus-malignancy effect,” as introduced by a scientist from Creative Biolabs, a biotech company offering minor histocompatibility antigen display service.

There are similarities between major and minor histocompatibility antigens. For example, MiHAs are bound to MHC I and MHC II antigens, and both are proteins present on the surface of the cells. They are all alloantigens, and immune responses are mediated by T cells for both types.

With so many similarities, differences do exist between major and minor histocompatibility antigens. MHC are glycoproteins that are present on the surface of all cells in order to present foreign antigens to immune cells while MiHAs are HLA-presented peptides derived from normal self-proteins. So, this is the key difference between major and minor histocompatibility antigens. MHC molecules are glycoproteins while MiHAs are small proteins. There are two classes of MHCs: MHC I and MHC II. MiHAs are diverse. Moreover, MHCs are coded by HLA genes while MiHAs are encoded by either autosomal chromosomes or by Y-chromosome.

Top 5 Biotechnology Industry Trends in 2023

As biotechnology continues to innovate and develop, many innovative technologies have gradually made significant breakthroughs after years of accumulation and in-depth research, which are expected to further break through the barriers to the development of existing technologies and achieve wider and better applications of technologies. The following 5 strategies will continue to grow and develop in 2023 to better the life science industry.

Big Data

Today, the biotechnology field has shown an unprecedented amount of data from the growing number of histology technologies and the integration of sensors and Internet of Things (IoT) devices. Big data and analytics solutions enable biotech startups to leverage this wealth of data to drive innovation. For example, it allows biopharmaceutical companies to more effectively recruit patients with certain requirements for clinical trials so as to push forward the potential drugs to the market.

Gene Editing

Genetic engineering has come a long way, from the random insertion of foreign DNA to precise editing in the genome. The increased efficiency of gene editing is due to the development of engineered nucleases and, more recently, CRISPR as molecular scissors. This has opened up applications in gene therapy for the treatment of genetic diseases as well as other diseases where gene editing techniques add, replace, or silence specific genes.

Gene Sequencing

Application areas where the gene sequencing industry has started to mature gradually include multi-omics research, population gene sequencing programs, new drug development and innovation, etc. In addition, there is still great potential for other application scenarios including agriculture, forestry and fisheries, as well as food safety. With the successive launch of higher-throughput gene sequencing-related devices and the continuous promotion of human genome projects in various countries, it is expected that the upgrading iteration will further reduce the sequencing cost and help gene sequencing to be used more in scientific research and clinical medicine.

Precision Medicine

The declining cost of gene editing and gene sequencing has made them more routinely used in clinical practice. It makes possible precision medicine, an approach that allows physicians to determine which treatment and prevention strategies are appropriate for specific groups. In addition, it enables personalized treatment for a wide range of diseases, including cancer. Biotech startups are using precision medicine to identify new drug targets, discover new drugs, deliver gene therapies, and develop new drug delivery technologies.

Artificial Intelligence

The definition of artificial intelligence (AI) covers a large number of technologies, including pattern recognition, predictive analytics, and deep learning. It enables biotech companies to streamline a variety of operational processes via enhanced automation. For example, a biotech company, Creative Biolabs, has launched an AI-based Antibody Discovery Platform to predict antibody-antigen binding and provide antibody drug candidates, which can typically generate 10 times more antibody sequence clusters than a laboratory-based approach alone.

While biotech advancements promise to transform global health, innovation is a complex undertaking. Several challenges, such as the high costs, regulatory concerns, and inadequate technologies, require more exploration.

Introduction to Immunoglobulin E And Its Future Research Directions

Immunoglobulin E (IgE) is an antibody—a protein produced by the immune system in response to a possible invader. It is primarily involved in the allergic response but also fights infections from parasites.

IgE is a Y-shaped protein, made of two light chains and two heavy chains of peptides (building blocks of protein). The heavy chains form the body and arms of the Y shape, and the light chains attach just to the arms of the Y shape. IgE binds to two types of receptors—high-affinity receptors and low-affinity receptors. The binding sets off a chain reaction that causes the cells to release chemical immune mediators, which are responsible for the symptoms of an allergic reaction, and it also triggers different effects in cells. For example, when IgE binds to a specific marker on B cells, it inhibits the synthesis of more IgE. This is called negative feedback and is how the immune system regulates itself.

The discovery of IgE in 1967 together with the identification of its central role in the pathogenesis of allergic inflammation has set the stage for the development of therapeutic anti-IgE strategies. The generation of detailed knowledge about the molecular and structural characteristics of IgE has further accelerated this process.

The first therapeutic anti-IgE antibody is rhuMAb-E25—today best known as omalizumab (Xolair®)—approved in 2003. This drug for subcutaneous use is an injectable prescription medicine used to treat moderate to severe persistent asthma in people 6 years of age and older, nasal polyps in people 18 years of age and older, hronic spontaneous urticaria (CSU) in people 12 years of age and older.

Monoclonal antibody solutions have so far dominated the anti-IgE biologicals industry, and several organizations have successfully advanced their anti-IgE prospects to the level of clinical trials. However, in the past 20 years, none of these have received therapeutic application approval.

Pre-clinical studies are now evaluating a number of innovative anti-IgE approaches based on the knowledge gained from earlier anti-IgE research. These next-generation anti-IgE variations aim to be either more specific than the conventional anti-IgE antibody approaches or to have multifunctionality, and some of them depart from the conventional monoclonal antibody framework.

To achieve the highest level of therapy performance, future anti-IgE biologicals would focus on aspects of targeting the involved pathomechanisms. Therefore, in addition to neutralizing free IgE, an ideal IgE inhibitor should actively disrupt IgE:Fc RI complexes on allergic effector cells and reduce the synthesis of IgE in B cells by binding to either mIgE, CD23-bound IgE, or inhibitory co-receptors. The development of several candidates has marked the beginning of multi-level targeting.

However, as clinical trials have demonstrated, there is still much room for improvement of such approaches. While recent studies clearly suggest that more tailored anti-IgE approaches for different indications are required, the question whether a universal anti-IgE biological that shows high treatment efficacy in a multitude of allergic disorders could be developed by broadening the activity profile and following a multi-level IgE targeting strategy remains to be investigated.

An Introduction to Intravenous Immunoglobulins and Natural Autoantibody

Human plasma is rich in a variety of antibodies including IgA, IgM, and IgG antibodies. Concentrated antibodies, known as intravenous immunoglobulins (IVIG), can be obtained from plasma by physical separation. IVIG contains a small amount of natural autoantibody.

Natural autoantibody (NAA), is a seminal part of the immune system originating from B1-cells and is mainly of the IgM isotype, with generally low binding affinity. They play important and diverse immunological roles, providing very early innate immune protection, ensuring removal of possible autoantigens by scavenging dead or apoptotic cellular debris, and possibly also improving cardiovascular profile.

This article will briefly introduce the current research and development trend of IVIG and NAA, and the comparisons between them.

The FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) have approved IVIG for clinical use. The low dose is indicated for the treatment of people with antibody deficiency, secondary hypovolemia, and recurrent bacterial infections. High doses are indicated for autoimmune diseases and infections, including idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. In addition, IVIG can be used clinically for more than 70 different disorders, including hematologic, dermatologic, and neuromuscular disorders. Clinical trials have also shown that IVIG may have anti-tumor growth and metastatic effects, and some studies have suggested that IVIG is a potentially useful adjuvant in anticoagulant therapy.

While NAAs are characterized by low affinity, non-specificity, and low chemotaxis. Early recognition of NAA was mainly based on IgM antibodies of ABO blood groups. With the development of science and technology, it has been found that NAAs also include IgG and IgA. Anti-VEGFR natural IgG antibodies have been found to inhibit the growth of cancer cells by inhibiting vascular endothelial growth factor receptor (VEGFR1), including liver cancer, pancreatic cancer, and nasopharyngeal cancer.

The characteristics of IVIG compared to anti-tumor NAA plasma are as follows.

1) They both present the risk of infection with blood diseases as they are derived from human plasma.

2) The affinity and specificity of them are both at a low level, and there are more adverse reactions with IVIG.

3) The batch variability in the production of IVIG and NAA plasma is relatively high.

4) The therapeutic effect of anti-tumor NAA plasma is yet to be evaluated. There is too little information on clinical trials.

5) It is very difficult to screen a large amount of anti-cancer NAAs from plasma as the percentage of people carrying these antibodies is extremely low. The targets currently used are not the most researched mature targets, and it is uncertain whether they will be effective in patients with advanced hepatocellular carcinoma and patients with metastatic tumors.

Over the past two decades, IVIg has become the preferred treatment for Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and Kawasaki disease. While the application of NAA in clinical treatment is still on the way. With the increasing understanding of the physiology of NAAs, scientists are exploring how to harness NAAs as a future therapy for autoimmune disorders.