Cancer has remained one of the leading causes of deaths worldwide. While chemotherapy and radiation have been used for decades to treat various cancer types, immunotherapy is emerging as a promising new approach with the potential to significantly improve survival rates. Immunotherapy, also called biologic therapy, is a type of cancer treatment that helps boost the body's natural defenses to fight cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.
CAR T-cell Therapy
One of the most promising types of Immunotherapy Drugs is called CAR T-cell therapy. It involves collecting T cells, a type of immune cell, from a patient's blood and genetically engineering them to recognize cancer cells. The engineered T cells are known as chimeric antigen receptor (CAR) T cells. Once infused back into the patient, these CAR T cells can target and destroy cancer cells that have been difficult to treat with other therapies. CAR T-cell therapy has shown remarkable success in treating certain blood cancers like acute lymphoblastic leukemia and lymphoma. In some clinical trials, over 80% of leukemia patients achieved complete remission within three months of treatment with CAR T cells. The therapy is now FDA approved for some leukemia and lymphoma patients who have not responded well to other treatments. However, CAR T-cell therapy is still not widely available and researching is ongoing to expand its use for solid tumors.
Checkpoint Inhibitors
Another major class of immunotherapy drugs are checkpoint inhibitors. Checkpoints are mechanisms in the immune system that act like brakes to prevent the immune system from attacking the body's own tissues. Some cancers take advantage of these brakes or checkpoints to avoid detection and destruction by the immune system. Checkpoint inhibitors work by releasing these brakes and allowing the immune system to recognize and destroy cancer cells again. Two checkpoint proteins that are commonly targeted are CTLA-4 and PD-1. Drugs blocking these checkpoints have shown significant benefits in treating various cancer types including melanoma, lung cancer, kidney cancer, head and neck cancer, Hodgkin's lymphoma and more. Ipilimumab was the first immune checkpoint inhibitor approved by the FDA in 2011 for treatment of advanced melanoma. Since then, drugs targeting PD-1 like pembrolizumab and nivolumab have been approved for use in multiple cancer types and lines of therapy based on improved survival benefits demonstrated in clinical trials. Checkpoint inhibitors have raised hopes as they can potentially provide long-term control over cancers. However, they may cause immune-related side effects as the immune system becomes overactivated in some patients. Extensive research continues to broaden the use of checkpoint inhibitors alone or in combination with other therapies.
Adoptive Cell Transfer
Another type of novel immunotherapy gaining prominence is adoptive cell transfer (ACT) therapy which also involves genetically engineering T cells. In ACT, T cells are extracted from a patient's tumor or blood and modified in the lab to express T cell receptors (TCRs) or CARs that enable them to recognize specific cancer antigens. The modified T cells are then grown and expanded in large numbers in the laboratory and infused back into the patient to seek out and destroy cancer cells. ACT utilizing tumor-infiltrating lymphocytes (TILs) has shown impressive outcomes in melanoma patients with overall response rates of over 50% in some trials. ACT holds great potential but widespread clinical use is limited by the complicated manufacturing process required to isolate, modify and expand T cells for each individual. Simplifying ACT manufacturing could help make this approach more accessible. Overall, ACT remains an area of active research with efforts focused on improving expansion methods and engineering T cells targeting different cancer antigens.
Oncolytic Viruses
A development branching out from immunotherapy is the use of oncolytic viruses - viruses that can selectively infect and kill cancer cells. Oncolytic viruses work through selective or conditional replication - they are genetically modified to selectively replicate inside cancer cells and not normal cells. As the viruses replicate, they cause the cancer cells to rupture and die, while spreading to neighboring cancer cells. This triggers anti-tumor immune responses in the body. Oncolytic viruses could offer a novel way to treat cancer by directly killing tumor cells as well as alerting the immune system. Oncolytic herpes and adenoviruses have shown promise in early clinical trials, with some patients experiencing tumor shrinkage or remission. Talimogene laherparepvec became the first oncolytic virus therapy approved by the FDA in 2015 for the treatment of melanoma. Many other oncolytic viruses are in clinical development for various cancer types, either alone or in combination with checkpoint inhibitors or radiation. Oncolytic virus therapy exemplifies the potential of developing 'living drugs' that can destroy cancer from within.
Combination Therapies
One of the most exciting areas in cancer immunotherapy research involves combining different immunotherapy drugs or combining immunotherapy with chemotherapy, radiation or targeted therapies. Using drug combinations often produces stronger and longer-lasting responses than single agents alone. For example, combining checkpoint inhibitors that target CTLA-4 and PD-1 has emerged as a very effective strategy for treating melanoma and lung cancer. Trials are also exploring adding immunotherapy earlier in conjunction with chemotherapy, which may help sensitize tumors to subsequent immunotherapy. Combination strategies are considered key to overcoming resistance and improving outcomes across more cancer types. Extensive clinical research is focused on identifying optimal immunotherapy combinations and sequencing for greatest synergy against cancer. Combination regimens also bring the challenge of managing cumulative toxicities, emphasizing the importance of biomarker development to select patients most likely to benefit.
Future Directions
Immunotherapy has revolutionized cancer treatment in a short span and offers hope for long-term disease control for patients who otherwise had very few options. The rapid pace of discovery has already established checkpoint inhibitors and CAR T-cell therapy as major breakthroughs. Looking ahead, further research seeks to broaden the number of cancer types that respond to immunotherapy, develop combination regimens with greater potency against difficult-to-treat cancers, and expand the pool of therapeutic vaccines, oncolytic viruses and other immunotherapies. There is also significant interest in combining immunotherapy with targeted therapies, to cover both immune escape mechanisms as well as direct tumor vulnerabilities. With continued exploration of immunotherapies targeting novel pathways and biomarkers to select optimal treatment approaches, the future holds promise of substantially improving survival and quality of life for cancer patients worldwide. Immunotherapy has undoubtedly sparked a new era in cancer treatment and its full potential is yet to be realized.
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