June 12, 2020
Keio University School of Medicine
A research group led by Project Professor Yutaka Kawakami, Visiting Lecturer Tomonori Taniguchi, and Collaborative Researcher Daiki Kato of the Institute for Advanced Medical Research, Keio University School of Medicine, in collaboration with Professor Tetsuji Naka and Associate Professor Satoshi Serada of Kochi University, has developed chimeric antigen receptor (CAR) T-cells targeting glypican-1, which is expressed in cancers such as squamous cell carcinoma. They demonstrated that these cells show high therapeutic efficacy against solid tumors without side effects in mice transplanted with human cancer cells. Furthermore, they discovered that even for cancers where the anti-PD-1 antibody, an immune checkpoint inhibitor, is less effective on its own, a high therapeutic effect can be achieved by combining it with CAR-T cells.
Immune checkpoint inhibitors, the subject of a Nobel Prize in Physiology or Medicine, have shown therapeutic effects against various cancers. However, many patients do not respond to this monotherapy, and how to treat these cases remains a challenge. Immune checkpoint inhibitors enhance the function of T-cells that attack cancer by releasing the "brakes" on the immune response, but they may be ineffective if the patient's body does not have enough of these T-cells. In such cases, expectations are high for "CAR-T cell therapy," in which T-cells that specifically recognize and attack cancer antigens are created through genetic engineering and then administered. However, while this method shows high therapeutic efficacy in hematologic cancers such as leukemia, it has not been sufficiently effective for solid tumors because effective target cancer antigens have not been identified.
This study, through animal experiments, demonstrated that glypican-1 is an effective target for CAR-T cell therapy in solid tumors. Furthermore, it showed that a combination therapy of glypican-1-targeting CAR-T cells and an anti-PD-1 antibody can achieve a strong therapeutic effect even against solid tumors that are resistant to anti-PD-1 antibodies. This is achieved through both the direct action of the CAR-T cells themselves and the indirect action of newly inducing cancer-attacking T-cells within the body.
The results of this research indicate the potential for clinical application of glypican-1-targeting CAR-T cell therapy for solid tumors.
This research was published in "eLife," a comprehensive journal of biomedical research, on March 31, 2020.
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