Engineered immune cells, called CARTmeso cells, designed to direct antitumor immune responses toward tumors that carry a protein called mesothelin, showed antitumor activity in two patients with advanced cancers that had not responded to prior treatments, according to a study published in Cancer Immunology Research, a journal of the American Association for Cancer Research.
Chimeric antigen receptor T cells (CAR T cells) are a form of personalized cell therapy that uses immune cells called T cells from patients. After T cells are harvested from a patient, they are engineered to bear a molecule that allows them to attach to a specific protein carried by the patient's cancer cells and to be triggered to kill the cancer cells when they do so. CAR T cells have shown early promising results for patients with some types of leukemia and lymphoma; however, they have not been very successful for solid cancers, one of the major issues being toxicity. Because normal cells express the CAR T cell target protein, albeit at lower levels than cancer cells, the engineered T cells recognize and attack the normal cells as well the cancer cells, causing off-target toxicity.
"So far, researchers have been permanently modifying T cells by using a variety of methods, including using viruses," said Carl H. June, M.D., a professor of pathology and laboratory medicine in the Perelman School of Medicine at the University of Pennsylvania and director of translational research in the university's Abramson Cancer Center.
"We engineered T cells to express a CAR for about three days, after which the mRNA is metabolized rapidly by the system, so the T cells basically revert to what they were before in the patient," explained June. "These T cells recognize a protein called mesothelin present in many tumors, including mesothelioma and pancreatic cancers, hence we named them CARTmeso cells. Our strategy is to give multiple infusions of CARTmeso cells to the patient, and if there is toxicity, we could abort the toxicity just by stopping the infusions, because the mRNA-based CARs rapidly revert to normal T cells."
"We found that the temporary CARs we engineered are safe, with no significant on-target, off-tumor toxicity," June added. "We have evidence of antitumor effects in two patients whose advanced tumors failed previous therapies. These results, albeit preliminary, are very promising."
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