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Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer

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Abstract

Cellular and targeted immunotherapies have revolutionized cancer treatments in the last several decades. Successful cellular therapies require both effective and durable cytotoxic activity from the immune cells as well as an accessible and susceptible response from targeted cancer cells. Correlative studies from clinical trials as well as real-world data from FDA-approved therapies have revealed invaluable insights about immune cell factors and cancer cell factors that impact rates of response and relapse to cellular therapies. This review focuses on the flagship cellular therapy of engineered chimeric antigen receptor T-cells (CAR-T cells). Within the CAR-T cell compartment, we discuss discoveries about T-cell phenotype, transcriptome, epigenetics, cytokine signaling, and metabolism that inform the cell manufacturing process to produce the most effective and durable CAR-T cells. Within the cancer cell compartment, we discuss mechanisms of resistance and relapse caused by mutations, alternative splicing, post-transcriptional modifications, and cellular reprogramming. Continued correlative and mechanistic studies are required to help us further optimize cellular therapies in a variety of malignancies.

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CY is supported by R38HL143615 from the National Institutes of Health. KLD is supported as the Anne T. and Robert M. Bass Endowed Faculty Scholar in Pediatric Cancer and Blood Diseases through the Stanford Maternal and Child Health Institute.

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  1. Department of Pediatrics, Division of Hematology, Oncology, Stem Cell Transplant and Regenerative Medicine, Stanford University, Stanford, CA, USA

    Catherine D. Yao & Kara L. Davis

  2. Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA

    Kara L. Davis

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Yao, C.D., Davis, K.L. Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer. Cancer Metastasis Rev 44, 15 (2025). https://doi.org/10.1007/s10555-024-10232-4

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