Abstract 5506: CD30 co-stimulatory domain enhances the efficacy of chimeric antigen receptor-engineered γδT cells

Adoptive transfer of immune killer cells genetically engineered to express chimeric antigen receptors (CARs) has demonstrated a feasible and effective approach against numerous types of cancers. Among the killer cells, γδT cells possessing a wide range of antigen-independent tumor recognition and low risk of developing GVHD offer a chance to develop CAR-engineered allogenic ‘off-the-shelf’ cellular therapeutics. Successful tumor eradication primarily depends on providing optimized signals affecting the proliferation, persistence, antitumor activity and cytokine secretion of CAR-γδT cells. We describe here a novel CD30 costimulatory domain for CAR signaling, which is known to be involved in cell anti-apoptosis, activation and proliferation. Conventional αβT cells and innate γδT cells activated by a CD30-ζ signaling-CAR displayed similar levels of cytolytic efficacies and cytokine secretion against antigen-expressing cancer cell lines as those of other CAR containing commonly used costimulatory domains CD28, CD27, 4-1BB, OX40, and ICOS. Furthermore, the third-generation CARs including the CD30 costimulatory domain retained potent antitumor efficacies independent of their position or type of partner costimulatory domain. More significantly, CAR-γδT cells containing CD30-ζ signaling revealed effective cytolytic activities against several solid cancer cell lines based on its antigen-recognizing antibody fragments. Our findings suggest that the CD30 costimulatory domain could be an attractive candidate for developing CAR-engineered killer cell therapeutics and may be applicable for the design of numerous antigen-recognizing CAR constructs, with an emphasis on targeting solid tumors. Citation Format: Hyun-Il Cho, Chung-Hyo Kang, Sang-Eun Lee, In-Sil Song, Jung-Min Ha, Seon-Duk Lee, Hyun-Jung Sohn, Tai-Gyu Kim. CD30 co-stimulatory domain enhances the efficacy of chimeric antigen receptor-engineered γδT cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5506.