Abstract 6353: Combination of poly-γ-glutamic acid with anti PD-L1 blockade leads to improved anti-tumor activity in murine models

Abstract

Abstract Immune checkpoint inhibitors(ICIs) have been shown to be key role in cancer therapy. Especially, antibodies targeting programmed cell death ligand1(PD-L1) promoted T cells to activate immune response against cancer cells. However, the current ICIs still have insignificant to motivate effective antitumor immunity by blocking PD-1/PD-L1 pathway and the regulatory network of PD-L1 by cytokines in the tumor microenvironment remains to be uncovered. Previously, we have reported the anti-cancer effects of combination treatment with a natural product, poly-γ-glutamic acid(γ-PGA), and PD-1 blockade. Now, we showed that combination therapy with anti PD-L1 and γ-PGA overcome the limits of ICIs and enhance anticancer effect in murine melanoma(B16F10). In vivo efficacy studies were performed by intraperitoneal injection of antibody targeting PD-L1 and oral administration of γ-PGA in C57BL/6 model transplanted with B16F10 melanoma cell. Systemic changes in immunophenotype were measured by tumor volume size and survival rate. The splenocytes were isolated from mice and the populations of myeloid-driven suppressor cells(MDSCs) and CD4/CD8 T cells were analyzed by FACS. Combination therapy with γ-PGA and anti PD-L1 blockade showed dramatically more suppressive tumor growth and enhanced long-term survival rate than other monotherapic treatment. In addition, γ-PGA was shown to play a role in the immune modulation of tumor microenvironment by activation of T cells and inhibition of MDSCs so as to prevent tumors from immune escape. Therefore, we suggest that γ-PGA can promote ICI-mediated antitumor responses by the transformation of "cold tumors" into “hot tumors” Citation Format: Jae-Pyung Jang, Jae Chul Choi, Kyung-Soo Hahm, Do Young Lee, Young-Chul Park. Combination of poly-γ-glutamic acid with anti PD-L1 blockade leads to improved anti-tumor activity in murine models [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 6353.