CAR T cells targeting Olfactory Receptor OR2H1 are an effective immunotherapeutic option in human epithelial tumors
BISWAS, S; Martin, A; Galindo, CMA; Mine, J; Payne, KK; Mandal, G; Chaurio, R; Powers, JJ; Sprenger, K; Rigolizzo, KE; Innamarato, P; Harro, C ...
Published in: The Journal of Immunology
Chimeric antigen receptor (CAR) T cells have been successful for hematological malignancies, but so far showed limited efficiency against solid tumors. Olfactory receptors are expressed in a variety of epithelial cancers, with a limited expression in healthy tissues. We quantified olfactory receptor OR2H1 expression in ovarian cancer, non-small cell lung cancer (NSCLC), breast cancer, and many normal tissues, and we found OR2H1 is expressed in multiple solid epithelial tumors but limited to testis among healthy human tissues. CAR T cells targeting OR2H1-extracellular domain were generated, and OR2H1-specific cytotoxic killing was confirmed, both in vitro and in vivo. Correspondingly, OR2H1-CAR T cells mediate significant therapeutic effects against OR2H1+ NSCLC and high-grade serous ovarian cancer. Interestingly, OR2H1 ablation significantly delays malignant progression of at least NSCLC, but OR2H1 expression is found to be essential for the cytotoxic effects of the OR2H1-CAR T cells. In summary, T cells directed against OR2H1-expressing tumor cells could be a potential therapeutic approach in future for treating OR2H1-expressing cancers.Supported by CA076292, R01CA157664, R01CA124515, R01CA178687, R01CA211913, U01CA232758