BCL-2 mutant B7H6-CAR-T cells synergized with venetoclax for treating small cell lung cancer

• DOI: 10.1136/jitc-2024-010073
• Publication Date: 2025-05-08T06:10:16Z
• Authors: Huihui Zhang; Liliang Xia; Wendi Xuzhang; Ziming Li; Junshi Zhang; Fanlin Li; Chen Cheng; Jiawen Wang; Xincheng Zong; Xuanming Yang; Shun Lu
• Keywords: Venetoclax

Background Patients with small cell lung cancer (SCLC) generally have a poor prognosis, an exceptionally high proliferative rate and strong propensity for early metastasis, indicating the urgent need novel therapies. The development of chimeric antigen receptor (CAR)s targeting solid tumors is limited owing to lack target antigens low efficacy. In this study, we aimed discover new targets SCLC CAR-T therapy develop CAR-T-based combinational treatment against in preclinical models. Methods vitro antitumor activity B7H6-specific was evaluated. Venetoclax-resistant B7H6 were designed synergistic effect venetoclax B7-H6 cells tested vivo. Result highly expressed tumors. displayed antigen-specific BCL-2(D103E)-expressing showed resistance venetoclax-induced apoptosis. B7H6-targeting potent anti-SCLC Conclusions Our findings suggest that combination BCL-2 mutant-expressing could be promising strategy B7H6-expressing SCLCs other tumors, providing foundation proapoptotic molecules patients clinical trial.