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Enhanced CAR-T Therapy Combats Solid Tumors

A discovery can potentially improve cancer treatments in the future and give patients another means to recover from cancer.

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        A discovery can potentially improve cancer treatments in the future and give patients another means to recover from cancer. 

        The study featured in Science Advances showed that researchers from Montefiore Einstein Comprehensive Cancer Center (MECCC), the designated National Cancer Institute based in New York, developed five CAR-T therapies. The fifth proved to be the most effective and could lead to higher survival rates. 

        Dr. Xingxing Zang, a member of the MECCC Cancer Therapeutics Research Program and the study’s senior author, explained how his team strengthened CAR-T cell therapy to create a formidable solution to solid tumors:

        “We wanted our CARs to not only attach T cells to solid tumors but also—by binding specifically to B7-H3—to prevent B7-H3 from interfering with the T cells’ ability to attack and destroy cancer cells and their blood vessels.”

        B7-H3 is a cancer cell antigen, discovered with the help of Dr. Zang, that allows tumors to evade immune attacks by interfering with T cell function. 

        However, the team realized that merely deactivating B7-H3 was insufficient for CAR-T therapies to combat solid tumors. Instead, they integrated a costimulatory protein called TMIGD2 to activate and boost T cells upon contact with cancer cells.

        “Factors such as low-oxygen levels and immune checkpoints inside solid tumors make for a hostile microenvironment that can strongly suppress immune attack by T cells—which also have trouble penetrating solid tumors’ dense connective tissue network. It seemed possible that using TMIGD2 as a costimulatory protein could give CAR-T cells the activation boost they need to reach cancer cells and persist within solid tumors,“ said Dr. Zang, who is also a professor and the founding director of MECCC’s Institute for Immunotherapy of Cancer at Albert Einstein College of Medicine. 

        When tested on mice, the CAR-T therapy containing both the novel antibody and the TMIGD2 protein, aptly called TOP CAR, successfully kept seven of the nine mice with glioblastoma alive. Only three out of nine mice that underwent any of the remaining CAR-T therapies survived.

        Dr. Zang and the team are planning a further study to assess the capabilities of TOP CAR in treating solid tumors other than those associated with lung, pancreatic, and glioblastoma cancers.

        Read the full article here to learn more about the science behind the development of TOP CAR.

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