A new approach to cancer immunotherapy that uses one type of immune cell to kill another — rather than directly attacking the cancer — provokes a robust anti-tumor immune response that shrinks ovarian, lung, and pancreatic tumors in preclinical disease models, according to researchers at the Icahn School of Medicine at Mount Sinai in New York. The findings were published October 11, 2022 in the journal Cancer Immunology Research.
The study involved a twist on a type of therapy that uses immune cells known as CAR T cells. CAR T cells in current clinical use are engineered to recognize cancer cells directly and have successfully treated several blood cancers. But there have been challenges that prevent their effective use in many solid tumors.
Most solid tumors are heavily infiltrated by a different type of immune cell called macrophages. Macrophages help tumors grow by blocking the entry of T cells into tumor tissue, which prevents CAR T cells and the patient’s own T cells from destroying the cancer cells.
To tackle this immune suppression at the source, the researchers engineered T cells to make a “chimeric antigen receptor” (CAR) that recognizes a molecule on the surface of macrophages. When these CAR T cells encountered a tumor macrophage, the CAR T cell became activated and killed the tumor macrophage.
Treatment of mice bearing ovarian, lung, and pancreatic tumors with these macrophage-targeting CAR T cells reduced the number of tumor macrophages, shrunk the tumors, and extended their survival.
The killing of tumor macrophages allowed the mouse’s own T cells to access and kill the cancer cells. The investigators further demonstrated that this anti-tumor immunity was driven by release of the cytokine interferon-gamma — a molecule involved in the regulation of inflammatory responses — from the CAR T cells.
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