Team Rejuvenates Exhausted T Cells to Successfully Produce T Cells with Strong Anti-tumor Effects: Development of a Novel CAR-T Cell Therapy for Cancer Immunotherapy
November 25, 2021
Keio University School of Medicine
A research team led by Professor Akihiko Yoshimura of the Department of Microbiology and Immunology at the Keio University School of Medicine has developed a simple method to rejuvenate exhausted T cells and induce T cells with strong anti-tumor effects, suitable for CAR (chimeric antigen receptor) -T cell therapy.
CAR-T cell therapy is a cancer treatment in which T cells derived from the peripheral blood of cancer patients are transferred back to the patients after introducing CAR, a gene that recognizes cancer cells. While T-cell therapies, including CAR-T cell therapy, have been attracting attention as effective cancer treatments, ex vivo expansion of T cells results in the "exhaustion" of T-cells, which reduces their anti-tumor effects. Therefore, various efforts have been made to "rejuvenate" exhausted T cells into young memory T cells, also known as stem cell-like memory T cells or TSCM. TSCM cells can actively divide and produce many daughter cells that can attack cancer. The method to convert exhausted T cells into TSCM cells, however, has not yet been established.
The research team successfully converted exhausted T cells into TSCM cells by culturing the CAR-T cells in the presence of a combination of four factors, namely IL-7, CXCL12, IGF-I, and NOTCH ligand, and named these cells CAR-iTSCM cells. CAR-iTSCM cells proliferate quickly in response to cancer cells, have a long lifespan, and exhibit stronger anti-tumor effects than conventional CAR-T cells.
The results of this research were recently published in Cancer Research Communications, a journal of the American Cancer Society.
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