Researchers from City of Hope\u00ae, one of the largest and most advanced cancer research and treatment organizations in the country, have developed a new “plug-and-play” technology that adds engineered molecules to chimeric antigen receptor (CAR) T cells after treatment, allowing scientists to better control the cells and redirect them to attack different types of cancer. Published this month in Cancer Immunology Research, a journal of the American Association for Cancer Research, the preclinical study offers a more flexible way to help CAR T cells keep pace with mutating tumors.<\/p>\n
CAR T cell therapy genetically reprograms a patient’s immune cells to seek out and kill cancer. The personalized approach has revolutionized treatment, yet today’s therapies remain largely “hardwired” and unable to adapt after the rewired cells are restored to the patient’s bloodstream.\u00a0<\/p>\n
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The bottom line is that tumors adapt to CAR T therapies, leading to treatment failure and cancer relapse. To remain effective, our therapies need to adapt, too. City of Hope has created a system that allows us to reconfigure these potent cancer killers as the tumor progresses.”<\/p>\n
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John Williams, Ph.D., co-senior author, director of City of Hope’s X-ray Crystallography Core<\/p>\n
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A solution to CAR T’s drawbacks<\/p>\n
While effective at treating blood cancers, CAR T therapies face several limitations. The treatments have a short lifespan, can cause serious side effects and can’t be altered after infusion. As tumors evolve and develop new ways to escape immune attack, CAR T cells<\/a> can lose their effectiveness, allowing some cancer cells to survive and drive relapse.<\/p>\n To overcome these hurdles, Dr. Williams collaborated with co-senior author Christine Brown, Ph.D., deputy director of T Cell Therapeutics Research Laboratories at City of Hope, to build on his earlier research on a technology called meditope*, a molecular “docking system” that allows scientists to add new capabilities to immunotherapies.<\/p>\n In the new study, the scientists redesigned CAR T cells so they could connect with a small molecule called meP, creating a new type of cell called meCAR T.<\/p>\n Next, the team showed that meCAR T cells could be equipped with different add-ons that help them be tracked, grow and recognize a wider range of cancer cells.<\/p>\n New platform delivers power and flexibility<\/p>\n “Much like a software update adds new features to a smartphone after you buy it, meditope allows us to send new instructions to CAR T cells already in the body,” said Dr. Williams, a professor in the Department of Cancer Biology and Molecular Medicine at Beckman Research Institute of City of Hope.<\/p>\n The team also showed that meCAR T cells could be programmed to carry out new functions, helping researchers better control how the cells find and attack cancer.<\/p>\n