Immunology is a field of biomedical science that involves the study of all aspects of the immune system in all organisms, both in the context of health and disease. Our immune system plays a critical role in safeguarding the human body from foreign pathogens and infections through a complex network of protective cellular pathways. Common conditions like allergies, cancer, and autoimmune diseases are the result of malfunctions within the immune system. However, there is a growing body of evidence suggesting that the immune system may also contribute to other diseases which have traditionally not been considered immunology in nature, such as Alzheimer’s disease. As a result, in recent years, the field of immunology – and, by extension, the use of immunotherapy, which uses the body’s own immune system to fight diseases – has made significant strides in treating a range of conditions.

In honor of International Immunology Day on April 29th, TFS HealthScience CRO (Contract Research Organization) is excited to spotlight the importance of this field and how immunology research is changing the lives of millions of patients worldwide. This article provides a comprehensive understanding of immunology and immunotherapy and highlights the top five recent innovations in immunotherapy that have revolutionized this field. Read on to learn more! 

 

Studying the Human Immune System: Four Key Branches of Immunology

The immune system, composed of molecular and cellular components, is divided into innate and adaptive immunity. Innate immunity is the first line of defense and is non-specific, including physical barriers and cells ready to protect against all pathogens. On the other hand, adaptive immunity, the second line of defense, builds memory of encountered infections to mount an enhanced, specific response. It involves antibodies and T cells, which target free-roaming pathogens and those that have colonized cells, respectively.

Studying immunology entails understanding how the body distinguishes between self and non-self and, accordingly, how it reacts to foreign pathogens. This information can be studied in a number of ways, giving rise to eight specific areas, including the following four key branches relevant to human disease:

 

1. Clinical Immunology: The study of types of diseases caused by immune system dysfunction, as well as the study of the process by which the immune system destroys transplants.
2. Immunochemistry: The study of analyzing the components and molecular mechanisms involved in the immune system, such as proteins (antigens) and antibodies, and their interactions.
3. Immunopathology: The study of how the immune system responds to various organisms in the body.
4. Immuno-Oncology: The study of harnessing the power of and enhancing the body’s own immune system to regulate, target, and combat cancer cells.  

 

Importance of Understanding the Immune System in Disease Treatment

The immune system consists of a highly regulated and delicately balanced nature that can lead to disease if disturbed. As stated earlier, malfunctions of the immune system play a role in several prevalent conditions, from allergies to cancer. Therefore, understanding how these processes take place through immunology research is vital for developing new therapies and treatments for these diseases, particularly those that have been traditionally difficult to treat. The following are examples of conditions that have benefited significantly from the contributions of immunologists and other immune system researchers:  

• Immunodeficiency disorders occur when the immune system’s ability to mount a defense against foreign bodies is impaired. Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is one of the most well-known examples of this type of disease. 
• Autoimmune diseases involve the immune system mistakenly viewing the host’s cells as foreign, resulting in attacking the body it is meant to protect. Examples include type 1 diabetes mellitus, multiple sclerosis, and systemic lupus erythematosus (SLE). 
• Allergies are a result of the immune system mounting a hypersensitivity response to harmless substances that are perceived as foreign pathogens, causing damage to the body’s tissues.  
• Transplants involve the immune system’s recognition of transplanted organs as foreign, making understanding immune responses critical for managing transplants and limiting rejection risk. 
• Vaccines leverage the immune system’s defenses to prime the body against weakened particles of pathogens to teach the body to recognize and defend itself against future exposure to specific infections.  

 

The Critical Role of Understanding Immunology in Oncology

Despite the immune system’s protective role, cancer cells can sometimes evade immune detection and destruction, leading to their uncontrolled growth and the formation of malignant tumors. This can occur through various mechanisms, such as the downregulation of antigen expression, which makes the cancer cells ‘invisible’ to the immune system. Another evasion strategy used by cancer cells involves the secretion of signaling molecules that suppress the immune response. Paradoxically, the immune system itself can also inadvertently promote tumorigenesis through chronic inflammation associated with autoimmune diseases or persistent infections, resulting in DNA damage and promoting the growth of cancer cells.  

 

How Immunotherapy is revolutionizing cancer treatment

Although immunology has been successfully applied to treat several immunologic conditions, no disease has been revolutionized to the extent that cancer treatment has with the introduction of immunotherapy. Immunotherapy is the concept of taking advantage of a patient’s own immune system to fight tumors. The benefits of immunotherapy over more traditional treatments based on chemotherapy alone primarily include its ability to reduce off-target adverse effects as a result of the more targeted approach. Treatments like chemotherapy or radiotherapy cannot distinguish between cancer cells and healthy cells, resulting in the latter being damaged during therapy. However, because immunotherapies target proteins or other markers specific to tumor cells, healthy cells are spared, and patients experience fewer side effects. This approach also supports personalized cancer therapy, wherein treatments are tailored to individual patients and their unique tumor presentation. As a result, immunotherapy has provided a new, safer, and more effective treatment option against several cancers, particularly those previously considered untreatable.  

 

Top Five Innovations in Immunotherapy

1. CAR-T cell therapy

This therapy involves genetically modifying a patient’s T cells to express a chimeric antigen receptor (CAR), which can bind to a specific protein on cancer cells to destroy them. Several advancements are being made to develop the next generation of CAR-T cell therapies. These include the advent of “off-the-shelf” CAR-T cells, as studied in the published UCART19 clinical trials, which are derived from healthy donors rather than the patient, significantly reducing the time and costs associated with this treatment. Researchers are also investigating the integration of switch receptors into CAR-T cell therapy to allow for better control of the therapy and minimize potential side effects.

 

2. Immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) work by blocking proteins that prevent immune cells from attacking cancer cells; by inhibiting these ‘checkpoints’, the immune system is freed to destroy tumors. For example, Drugs like pembrolizumab and nivolumab, which block the programmed death-1 (PD-1) protein, have shown remarkable efficacy in treating several types of cancer, including lung cancer and melanoma. PD-1 has become a key target in immuno-oncotherapy as it is often overexpressed in cancer cells, helping them evade the immune system. Another similar protein implicated in tumor evasion is CTLA-4, which another approved ICI, ipilimumab, functions to inhibit.

 

3. Cancer vaccines

These vaccines are designed to teach the immune system to recognize cancer cells as threats, thereby inducing an immune response against them. Unlike conventional vaccines, which prevent diseases, cancer vaccines are typically used as a form of treatment. For example, pivotal clinical trials have identified MZ2-E and MZ2-D, melanoma-derived antigens encoded by the MAGE gene family, which have been shown to effectively trigger antitumor immune responses. Dendritic cell (DC)-based vaccination is another exciting new avenue of research showing promising clinical outcomes, as evidenced by sipuleucel-T, a dendritic cell-based immunotherapy approved for the treatment of advanced prostate cancer.

 

4. Oncolytic virus therapy

This type of therapy employs genetically modified viruses that can infect and kill cancer cells, while leaving healthy cells unharmed. As of 2022, a total of four oncolytic virotherapy products have been approved for marketing: Rigvir (SND005), Oncorine (H101), Imlygic (Talimogene laherparepvec, T-VEC), and Delytact (teserpaturev/G47Δ). Lin et al. (2023) also reported a total of 329 clinical trials pursuing oncolytic viruses as monotherapy and as combination therapies were registered in ClinicalTrials.gov, with over 50% being in phase I of clinical testing.

 

5. Bispecific antibody-based tumor immunotherapy

These therapies rely on specially engineered antibodies that can bind to two different antigens at the same time, thereby enhancing their effectiveness against cancer cells. An emerging development in this area of drugs includes trispecific or trivalent antibodies, which are designed with three different binding sites. The result is a potential increase in the efficacy of cancer treatment with this multi-target approach. Additionally, prodrugs or inactive forms of bispecific antibodies that can be activated in the tumor microenvironment are being investigated to improve safety outcomes with such a localized activation approach.  

 

Conclusion

In conclusion, these top five innovations in immunotherapy represent only the surface of how advancing our understanding of the immune system is revolutionizing the way we approach disease treatment. All these therapies and more have shown tremendous promise in improving clinical outcomes and enhancing patient quality of life. Therefore, as our grasp of immunology and the new era of research in this field continues to discover breakthroughs, we can anticipate the emergence of even more innovative and effective therapies for immunologic diseases.

On April 29th, join TFS HealthScience CRO as we celebrate these groundbreaking innovations in honor of International Immunology Day! 

 

About TFS HealthScience CRO’s Immunology Team

Experience the difference with TFS HealthScience Dermatology, Immunology & Inflammatory Diseases CRO for your next immunology clinical trial! With a global mindset and local understanding, we provide a comprehensive suite of services, including study protocol design, medical monitoring, and project delivery. Our experienced teams and innovative technology ensure efficient delivery, no matter the complexity. As a full-service CRO, we’re proud to hold a track record of over 250 successful DIID studies conducted across 20+ countries and to have an established global network of over 6,000+ sites.

Trust TFS HealthScience to take your study to the next level with our dedicated Immunology leadership, led by the esteemed Ina Zschocke, Vice President Head of Dermatology, Immunology & Inflammatory Disease. Visit our website to learn more about the robust data-driven solutions TFS can offer for your next immunology clinical trial, or connect with a TFS representative here!