The next generation of CAR T cell therapies includes cancer inhibitors

Mondo Health Updated on 2024-03-05

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Label: T cell

Researchers at the University of Pennsylvania report that a variant of the p53 protein may increase the effectiveness of chimeric antigen receptor (CAR) T cells**.

researchers at the university of pennsylvania report a variant of the p53 protein may improve the effectiveness of chimeric antigen receptor (car) t cell therapy.

The findings were published in the Proceedings of the National Academy of Sciences of the United States of America, by Richard W., Department of Immunology, Department of Pathology and Laboratory MedicineLed by Professor Vague, Dr. Carl June, Director of the Center for Cellular Immunity** at the Perelman School of Medicine and Director of the Park Institute for Cancer Immuno** at the University of Pennsylvania.

the findings are published in the proceedings of the national academy of sciences and led by carl june, md, the richard w. vague professor in immunotherapy in the department of pathology and laboratory medicine, director of the center for cellular immunotherapies at the perelman school of medicine, and director of the parker institute for cancer immunotherapy at the university of pennsylvania.

"CAR T-cells, a **transformative form of blood cancers**, are limited by T-cell dysfunction, especially in chronic lymphocytic leukemia (CLL)," the researchers wrote. ”。Our study reveals the critical role of human and ape-specific p53 isoform δ133p53 in enhancing the effects of CAR T cells**. Expression of δ133P53A in CAR T lymphocytes can improve their metabolic robustness, giving them superior antitumor functions, especially under high tumor burden conditions. ”

car t cell therapy, a transformative treatment for blood cancers, is limited by t cell dysfunction, especially in chronic lymphocytic leukemia (cll),”the researchers wrote. “our study reveals a pivotal role for the human and great ape-specific p53 isoform, δ133p53α, in enhancing the therapeutic efficacy of car t cells. expressing δ133p53α in car t cells improves their metabolic robustness, enabling superior antitumor function particularly under high tumor burden conditions.”

June and colleagues targeted the p53 protein variant δ133p53, whose expression in human T cells decreases with age.

june and colleagues targeted the p53 protein variant δ133p53α, which decreases in expression with age in human t cells.

Sustained expression of 133p53 improved the anti-tumor function of CAR T lymphocytes made from healthy normal donors and CLL patients who were refractory to CAR T cells** in clinical trials. Expression of δ133p53 in CAR T cells enhances cellular metabolic function and enhances antitumor activity, especially under conditions of high tumor burden. Under trophic restriction conditions, CAR T cells expressing δ133P53 not only cleared more tumors, but also proliferated more, in part due to enhanced key biosynthetic processes and improved mitochondrial function.

continual expression of δ133p53α improved the antitumor function of car t cells manufactured from both healthy normal donors and from people with cll who failed to respond to car t cell therapy during clinical trials. expressing δ133p53α in car t cells enhanced the cells’ metabolic function, boosting antitumor activity, especially under conditions of high tumor burden. under nutrient-limiting conditions, car t cells expressing δ133p53α not only cleared significantly more tumor but also displayed increased proliferation, partly due to the enhancement of key biosynthetic processes and improved mitochondrial function.

These findings point to the important role of the p53 signaling network as a regulator of prolonging CAR T cell responses and provide a new pathway for the utilization of anticancer T cells.

the findings point to the significant role of the p53 signaling network as a regulator of prolonged car t cell responses and provides new **enues of therapies that harness cancer-fighting t cell

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