Target cell killing effects of CD20 targeting chimeric antigen receptor T cells derived from the type II anti-CD20 antibody.

• DOI: 10.1200/jco.2017.35.15_suppl.e14548
• Publication Date: 2018-09-06T15:42:53Z
• Authors: Yihong Yao; Xin Yao; Shigui Zhu; Wei Zhu; Zhiyuan Li; Qingxia Wang; Lin Zhu; Anyun Ma; Yanfeng Li; Yutian Wei; Chengxiang Dai; Li Zhang; Jiaqi Huang; Bizuo Liu
• Keywords: Ofatumumab; Obinutuzumab

e14548 Background: Chimeric Antigen Receptor T cells (CAR-Ts) targeting CD19 have shown very promising clinical outcomes in treatment of B-cell linage hematological malignancies. However, many patients with relapsed diseases were found to down-regulated/loss surface expression after CAR-T therapy. To solve this issue single-targeting escape, we explored the application another antigen, CD20, for targeted Methods: We constructed four CD20 CARs (all 4-1BB co-stimulatory signaling) base on single-chain variable fragments (scFV) derived from well-studied specific antibodies: Leu16, Rituximab, Obinutuzumab, and Ofatumumab. Obinutuzumab belong type I anti-CD20 antibody family appear bind different epitopes located large loop whereas Ofatumumab is II which has been interact hydrophobic residues small surrounding a deep binding cleft. Results: All can specifically recognized positive target our pre-clinical studies. They all showed up-regulated antigen-specific cell activation high level IFN-g release upon stimulation, CAR-T20-Ofatumumab appeared significantly higher more than 2-fold increase compared other three CAR-T20 their scFVs deriving antibodies. also degranulation it displayed ~50% ability kill cytotoxicity assays. Conclusions: Our data suggested that better vitro function appears be CAR superior those A possible explanation observation interacts loop, close membrane confers extensive striking slow off-rate. results suggest CAR-Ts may killing effects.