Bibliographic Details
| Title: |
Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity. |
| Authors: |
Vogt, Kristen C.1,2,3, Silberman, Pedro C.1,2,4, Qianqian Lin1,2,5, Han, James E.1, Laflin, Amy6, Gellineau, Hendryck A.1, Heller, Daniel A.1,2,3,4, Scheinberg, David A.1,2,3,4 scheinbd@mskcc.org |
| Source: |
Science Advances. 1/24/2025, Vol. 11 Issue 4, p1-16. 16p. |
| Subject Terms: |
*SYNTHETIC receptors, *TUMOR antigens, *CHIMERIC antigen receptors, *TUMOR-infiltrating immune cells, *CANCER cells, *T cells |
| Abstract: |
A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2+ normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature. These tumor microenvironment actuated T (MEAT) cells ameliorated T cell infiltration in the brain, preventing fatal neurotoxicity while maintaining antitumor efficacy. We found that conditional CAR expression improved the persistence of tumor-infiltrating lymphocytes because of enhanced metabolic fitness of MEAT cells and the infusion of a less differentiated product. This approach increases the repertoire of targetable solid tumor antigens by restricting CAR expression and subsequent killing to cancer cells only and provides a proof-of-concept model for other targets. [ABSTRACT FROM AUTHOR] |
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| Database: |
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