Abstract 2811: CT120, a novel fully human anti-CD19 x anti-CD22 dual targeted chimeric antigen receptor T cell product for the treatment of B-NHL and B-ALL

Abstract

Abstract Background: Anti-CD19 chimeric antigen receptor T cell therapies (CAR-T) have shown impressive clinical outcomes in relapsed/refractory (R/R) CD19+ B-cell non-Hodgkin lymphomas (B-NHL) and acute lymphoblastic leukemias (B-ALL). However, 30%-60% of patients with B-ALL who initially responded to anti-CD19 CAR-T therapies relapsed either due to poor CAR-T persistence or CD19 antigen escape, and preliminary data also indicated CD19 antigen loss in patients with B-NHL relapsed after anti-CD19 CAR-T therapy. In addition, the immunogenicity of murine origin CAR construct is another cause of limited in vivo CAR-T persistence. Design: To overcome these problems, a novel fully human anti-CD19×anti-CD22 dual targeted CAR-T cell product - CT120, has been developed. The CT120 CAR molecule contains tandem fusion of anti-CD19 and anti-CD22 scFv, which can effectively recognize CD19 and CD22 antigen independently, to avoid antigen escape. The intracellular CAR domain contains CD3ζ and 4-1BB co-stimulatory domain, which can improve in vivo persistence. In addition, both anti-CD19 and anti-CD22 antibody were generated from proprietary fully human libraries to minimize possible immunogenicity. The CAR molecule was transferred to autologous T cells through a lentiviral backbone. Results: The anti-CD19 and anti-CD22 scFv binds to its antigen in nanomolar range, and CT120 CAR-T cells can bind to both CD19 and CD22 antigens in a noncompetitive manner. CT120 CAR-T cells showed potent in vitro cytotoxicity not only to target B-cell lymphoma/leukemia cell lines (Raji, Daudi, and NALM-6), but also to the CD19 knockout (CD19-CD22+) and CD22 knockout (CD19+CD22-) Raji cell lines. CT120 can secret multiple cytokines, such as IL-2, TNF-α and IFN-γ, and proliferate efficiently after engagement of target cells. In vivo efficacy study demonstrated that CT120 CAR-T cells expanded effectively in mice and completely inhibit Raji and NALM-6 tumor cell growth. Furthermore, CT120 showed a favorable safety profile and promising efficacy in patients with r/r B-NHL and B-ALL in an investigator-initiated trial (IIT). Certain patients who relapsed after previous murine origin CAR-T treatment also benefited from CT120 therapy. Conclusion: Collectively, CT120 is a potent and safe anti-CD19×anti-CD22 dual target CAR-T product for the treatment of B-NHL and B-ALL, and now it is in registered phase 1/2 clinical trial. Citation Format: Panpan Niu, Qianli Hu, Jialu Mo, Guangrong Meng, Xiangyin Jia, Wei Cheng, Qiaoe Wei, Zhenyu Dai, Xuefeng Wu, Guang Hu, Taochao Tan, Jianfeng Zhou, Yongkun Yang, gang Hu. CT120, a novel fully human anti-CD19 x anti-CD22 dual targeted chimeric antigen receptor T cell product for the treatment of B-NHL and B-ALL [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 2811.