THE POWER WITHIN
FIGHTING CANCER WITH ADOPTIVE CELL THERAPY
By
XIYA WU SWATHI BALAJI
In 2012, a clinical trial made headlines throughout the nation as 7-year-old Emily Whitehead became the first pediatric patient to undergo T-cell therapy. For Emily, CAR T-cell therapy was a last resort, after chemotherapy had twice resulted in relapse. The weeks following the reintroduction of the engineered T-cells into her veins were difficult. She developed a high-grade fever and her blood pressure dropped dangerously in what we now know are the effects of an inflammatory response known as cytokine release syndrome (CRS)3. Ultimately, the treatment was a success, paving the way for T-cell therapy to be recognized as one of the most promising fields in the future of cancer treatment. In the last decade, adoptive cell therapy (ACT) has taken the world of cancer treatment research by storm. A type of ACT, CAR T-cell therapy has made remarkable strides from its use in small clinical trials
Emily Whitehead and her mother Kari Whitehead. Taken by Jeff Swensen for the New York Times4.
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to its use in the United States as the first type of gene-based therapy approved by the Food and Drug Administration (FDA)1. At the core of ACT is the idea of harnessing the patient’s own immune system to fight against cancer. For the standard cold or flu, the immune cells in our bodies are usually able to mount a highly effective response, and the accompanying symptoms are only temporarily uncomfortable. More impressively, the immune system has memory of the diseases it has encountered before. If the same virus comes knocking again, the secondary response from the immune system is both faster and stronger because the accumulated memory cells "remember" the antigens in question. Recognition of outsiders is crucial to the immune system's function. To prevent our immune system from turning on the body, immune cells must be able to distinguish "self " from "non-self." Failure to do so is what results in autoimmune diseases, where the immune system launches an immune response against its own antigens. Cancer, however, hinges on the opposite problem. Because cancer cells are the descendants of our normal cells, they can evade the immune system by disguising themselves as "self " despite their existence being harmful to the body. They are wolves in sheep's clothing. T-cell therapy, then, involves the shearing away of this disguise. Researchers generate CAR T-cells by genetically engineering the patient’s T-cells to produce chimeric antigen receptors (CARs) on the cell surfaces1. Like the Greek Chimera that existed as a hybrid of animal forms, these receptors are a fusion of different components decided by the researcher. The modified cells are then reintroduced into the patient and allowed to proliferate, truly earning them
