2017 was a watershed year, with the recent approval of chimeric antigen receptor (CAR)-T cell therapy for acute leukemia (tisagenlecleucel) and lymphoma (axicabtagene ciloleucel), as well as a number of new indications for already-approved immune checkpoint inhibitors.

Many expect that genetically engineered T cells and other immune cells combined with other forms of immunotherapy will revolutionize the treatment of cancer in ways unimaginable to scientists and clinicians only a few decades ago.

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Yet in unleashing the immune system to destroy cancer, we often endanger normal cells sharing antigens with cancers and other bystanders in the tumor microenvironment; we are therefore faced with the consequences of this process — autoimmune diseases — which can affect various sites including the skin, lungs, intestines, liver, endocrine glands, and nervous system. The need to control or prevent these immune-related adverse events adds to the complexity and potential toxicity of treatment.

More than 300 CAR-T studies are listed on ClinicalTrials.gov for tumor types ranging from acute leukemia and lymphoma to gastric, hepatic, pancreatic, lung, cervical, ovarian, colorectal, and brain cancers. But patients are typically hospitalized during therapy because of concerns about cytokine release syndrome.

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Another approach with great potential is immunotherapy specific to cancer/testis antigens, which have a highly restricted distribution. Antigens such as NY-ESO-1, with its broad expression in various cancers, is being studied in clinical trials.10,11 In the next decade or 2, I would expect that “off-the-shelf” immunotherapy regimens, including combined cellular therapy, monoclonal antibodies, cytokines, and other targeted therapies will be used to treat cancers with specific genetic mutations safely and effectively.

The future is bright for immunotherapy. As we learn to target the immune response to “self and non-self,” a delicate therapy balance will eventually be achieved with predictable outcomes, benefits, and toxicity in the fight against cancer.


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