In modern times, immunotherapy has revolutionized medical treatment and is being used to address a wide spectrum of diseases, offering new hope and effective treatment methodologies. Unlike traditional treatment methods that directly interact with the disease-causing agents, immunotherapy alters one’s own immune system to empower the body’s natural defense mechanisms for health restoration. Immunotherapy does this either by boosting an inadequate immune response or by suppressing an overactive or misdirected one1.
Immunotherapy relies on a complex network of cells, tissues, and organs that defend the body against foreign molecules and internal threats. This network includes key players such as T-cells, B-cells, macrophages, natural killer cells, and antibodies. They all work in a synchronized manner to identify and eliminate anything considered “non-self” or harmful. Normally, the body’s immune system performs exceptionally well to detect, fight off infections, and even destroy precancerous cells. When the immune system either becomes too weak to recognize a threat or mistakenly attacks healthy tissues, it can cause severe abnormalities or diseases. Immunotherapy aims to correct these dysfunctions.
Diverse Applications
Due to its significant impact on cancer treatments, immunotherapy has garnered significant attention on a much broader medical landscape.
Immunotherapy for cancer
In cancer, the body’s immune system often fails to recognize and thus effectively eliminate cancer cells. This allows them to evade the surveillance of the immune system. Cancer immunotherapy aims to overcome these evasive tactics, empowering the immune system to identify, target, and destroy malignant cells.
Immune checkpoint inhibitors
These drugs target the immune cells, particularly T-cells, helping them to effectively recognize and attack cancerous cells2. They work by blocking expressions of proteins like PD-1, PD-L1, or CTLA-4. These therapies have revolutionized the treatment of melanoma, lung cancer, kidney cancer, and other similar conditions.
CAR T-Cell Therapy
This involves genetically engineered T cells (patients’ own T cells) expressing Chimeric Antigen Receptors (CARs) that specifically target cancer cells3. This has shown remarkable success in certain blood cancers like aggressive lymphomas and leukemias.
Therapeutic monoclonal antibodies
These are engineered antibodies that can directly target cancer cells4. Their mechanism of action involves blocking growth signals or marking them for destruction by other immune cells.
Cancer vaccines
These aim to stimulate immune response. While preventative vaccines (like the HPV vaccine) are highly successful, therapeutic cancer vaccines for existing cancers are an active area of research5.
Oncolytic viruses
Oncolytic viruses are genetically modified viruses that selectively infect and destroy cancer cells6. Simultaneously they also stimulate an immune response against the tumor6.
Immunotherapy for autoimmune diseases
In autoimmune diseases, the immune system mistakenly identifies the body’s own healthy tissues as foreign objects and initiates an attack. Immunotherapy in this context focuses on suppressing the immune system to prevent this self-destruction. Some of the treatment methods include:
Targeted Biologics (Monoclonal Antibodies)
In conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, and multiple sclerosis, treatment strategies involve using targeted biologics or monoclonal antibodies. These highly specific drugs block key inflammatory molecules (cytokines like TNF-alpha, IL-6, IL-17) or deplete specific immune cell populations (like B-cells), thereby reducing inflammation and tissue damage7.
Immunosuppressants
These drugs reduce or suppress the immune system8. While older, broader immunosuppressants exist, newer immunotherapies offer more targeted approaches to modulate the immune response. Examples include corticosteroids, calcineurin inhibitors, etc.
Emerging cell therapies
This involves introducing living cells into a patient’s body to replace, repair, or enhance the function of diseased or damaged tissues, or to modulate the immune system. Research is exploring the use of regulatory T-cells to induce immune tolerance and halt autoimmune attacks9.
Immunotherapy for allergic diseases
Allergies occur when our immune system reacts to otherwise harmless substances (allergens). Immunotherapy aims to desensitize the body to these allergens, thus reducing the severity of allergic reactions.
Allergen immunotherapy
This involves gradual exposure to increasing doses of the allergen, which builds the immune system’s tolerance over time and shifts its response away from the problematic IgE antibodies10. This is effective for allergic rhinitis (hay fever), allergic asthma, and insect sting allergies.
Monoclonal antibodies
Some antibodies are designed to block key mediators of allergic reactions, such as IgE, providing relief for severe asthma and chronic hives11.
Immunotherapy for infectious diseases
Immunotherapy also plays a crucial role in preventing and treating infectious diseases by enhancing the body’s natural defenses against pathogens.
Vaccines (Prophylactic)
One of the oldest and most effective treatment methods involves the use of vaccines. They prime the immune system to recognize and remember specific pathogens before exposure, preventing infection12. Examples include measles, polio, influenza, and COVID-19 vaccines.
Therapeutic vaccines
For chronic infections like HIV or hepatitis B/C, research is ongoing to develop vaccines that can boost the immune system to recognize and clear existing infections13.
Monoclonal antibodies (passive immunization)
An immediate, temporary immunity can be achieved by directly supplying antibodies to neutralize pathogens or their toxins. These are utilized in the treatment of respiratory syncytial virus in infants or certain severe viral infections14.
Adoptive cell therapies
Transferring immune cells with specific anti-pathogen activity can be used to treat severe infections in immunocompromised patients, such as cytomegalovirus infection in transplant recipients15.
Advantages and challenges
Immunotherapy has the advantage of targeting disease-specific pathways with less collateral damage to healthy tissues. It can lead to durable and long-lasting responses, sometimes even after treatment cessation, due to the establishment of immune memory16. Such specificity of immunotherapy has opened doors as novel treatment options for diseases previously lacking effective therapies.
However, immunotherapy has challenges too.
- Modulating the immune system involves the risk of immune-related adverse events (irAEs), where the altered immune system can mistakenly attack healthy organs or tissues17. Thus, careful monitoring and management are always mandatory for patients undergoing immunotherapy.
- Response rates vary widely among patients, and predicting who will respond to immunotherapy remains a key area of research18.
- Some diseases can develop acquired resistance over time19.
- The high cost of many advanced immunotherapies also presents an accessibility barrier20.
Disease modeling, by providing predictive platforms for drug screening and biomarker identification, is increasingly being used to accelerate immunotherapy development and overcome some of these challenges.
The future of immunotherapy
The field of immunotherapy is rapidly evolving. Current research focuses on combination therapies that include integrating different immunotherapies with conventional treatments to achieve synergistic effects21. One of these aspects involves identifying one’s unique immune profile and disease characteristics and designing a personalized treatment approach22. Additionally, researchers are continually discovering novel immune targets and mechanisms to exploit, while simultaneously working to improve the safety and efficacy of existing therapies23. This helps to expand the reach of immunotherapy, offering hope for complex diseases such as neurodegenerative disorders24.
In conclusion, immunotherapy represents a transformative era in medicine that holds immense power and offers a precise approach in the treatment of a vast array of diseases. This can fundamentally change the outlook for countless patients worldwide.