Abstract 6314: Potent inhibition of tumor relapse after anti-HER2 affibody tagged with cotinine (switch) plus anti-cotinine switchable CAR T cell therapy by repeated re-injection of the switch

Abstract Chimeric antigen receptor (CAR) T cells targeting CD19 or the B cell maturation antigen (BCMA) have demonstrated impressive initial clinical responses. However, on follow-up assessment, a notable fraction of the patients with significant initial clinical response eventually experienced relapse. CAR T cell therapies targeting solid tumors have shown an even lower rate of clinical response as well as shorter remission periods. A prior study has shown that re-injection of the anti-HER2 CAR T cells was effective in a rhabdomyosarcoma relapse patient (Cancer Res 79, LB147 (2019) ), but the repeated production of CAR T cells is costly, thus raising questions about its feasibility in practice. Previously, we developed a cotinine-based CAR T cell system (zCART) comprised of a tumor antigen-specific affibody conjugated with cotinine and an anti-cotinine scFv CAR, and demonstrated the anti-tumor activity of an anti-HER2 zCART treatment in both in vitro and in vivo settings. In this study, we tested the efficacy of anti-HER2 zCART treatment in vivo using an intraperitoneal (IP) tumor model with a single infusion of zCART cells. The anti-HER2 switch was injected daily for 7 days. When the HER2 positive tumor relapsed, the mice were re-treated with the same dose of anti-HER2 switch treatment for an additional 7 days. We observed that re-injection of only the anti-HER2 switch and not combined with zCART cells effectively and potently inhibited relapse of HER2 positive tumors. Furthermore, the efficacy of the anti-HER2 switch re-injection treatment was maintained in one additional relapse. In summary, the zCART system has potential to treat cancer relapse following CAR T cell therapy without the need for an additional production round of CAR T cells. Citation Format: Ki Hyun Kim, Soohwan Kim, Eun-Hoe Lee, Soo-Yoon Lim, Sung Min Kim, E-Young Kim, Hyun-Jong Lee, Seong Yeol Kim, Min Yoon, Young-Ha Lee, In-Sik Hwang, Yoon Lee, Jong-Hoon Kim, Jong-Seo Lee, Junho Chung. Potent inhibition of tumor relapse after anti-HER2 affibody tagged with cotinine (switch) plus anti-cotinine switchable CAR T cell therapy by repeated re-injection of the switch abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6314.