Science Highlights
Published on September 30, 2025
Development of a human ENG CAR T to treat advanced sarcomas
by Cancer Immunology Research
Berger HR, Maharana M, Mirabel J, et al. Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas. Cancer Immunology Research. 2025; (doi: 10.1158/2326-6066.CIR-24-0897).
Researchers believe endoglin (ENG), with its capacity to deliver comprehensive tumor targeting, could advance the use of chimeric antigen receptor (CAR) T-cell therapy to treat advanced sarcomas. A dearth of effectual targets currently limits CAR T application in this setting; but ENG's expression on various sarcomas, cancer-associated fibroblasts, and neoangiogenic vessels raises its profile as a therapeutic candidate. Moreover, previous work has demonstrated that ENG knockout in sarcoma cells tempers their invasive behavior. In the current study, an ENG CAR T construct resolved key challenges associated with sarcoma CAR T therapy — tumor compactness and the stromal barrier created by cancer-associated fibroblasts — by disrupting multicellular tumor spheroids in vitro. The intervention also achieved robust antigen-specific cytokine release, substantial proliferation, memory formation, and cytotoxic function against various sarcoma cell lines. In mouse models, the novel CAR achieved control of tumor growth and metastasis, thereby prolonging the life of lab subjects.
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Cancer Immunology Research