LAUSR

Tumor homing of adoptively transferred cytotoxic T cells (CTLs) to solid tumors is still inefficient. In addition, CTLs that arrive at tumor tissues meet the immune-suppressive tumor microenvironment. To reduce these limitations in adoptive T-cell therapy against solid tumors, we here exploited CTLs dual-labeled with IL-4 receptor (IL4R)-targeting peptide and programmed cell death-ligand 1 (PD-L1)-blocking peptide. IL4R is commonly upregulated in many solid tumors including lung tumor. PD-L1, an immune checkpoint, is frequently upregulated in tumor cells and contributes to the suppression of CTLs in the tumor microenvironment. CTLs were isolated from the splenocytes of LLC lung tumor-bearing mice and non-genetically labeled with IL4RPep-1, an IL4R-targeting peptide, and PD-L1Pep2, a PD-L1-blocking peptide, using a sulfhydryl-reactive cross linker. Compared to unlabeled CTLs, IL4R-targeted, PD-L1-blocking CTLs showed more robust cytokine secretion and tumor cell lysis during co-culture with LLC tumor cells. The CTLs armed with the dual-acting peptides exerted higher levels of tumor homing and anti-tumor growth activity in LLC lung tumor-bearing mice, which was accompanied by decrease of immune-suppressive cells in the tumor tissues. These results suggest that the IL4R-targeted, PD-L1-blocking CTLs can be a promising strategy in adoptive T-cell therapy against solid tumors. Key words: Adoptive T-cell therapy, CTLs, IL-4 receptor, lung tumor, PD-L1 Citation Format: Dong Gyun Jo, Gunassekaran Gowri Rangaswamy, Poongkavithai Vadevoo Sri Murugan, Byungheon Lee. Cytotoxic T cells armed with IL-4 receptor-targeting and PD-L1-blocking peptides inhibits lung tumor growth. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4107.