Abstract B103: Attenuated <i>Salmonella</i> secreting interleukin-21 activates T-cells and induces anti-tumor effects

Abstract The tumor microenvironment is often characterized by an immunosuppressive state, limiting the efficacy of immunotherapies. Although blocking programmed death-1 (PD-1) and its ligand (PD-L1) can activate the immune system, its clinical success is often limited, prompting the exploration of combination therapies. Recent research has renewed interest in using attenuated Salmonella strains as cancer therapeutics due to their ability to target tumors, stimulate immune responses, and promote tumor cell death, though complete tumor eradication remains a challenge. In this study, we aimed to enhance anti-tumor immunity by leveraging Salmonella-mediated delivery of interleukin-21 (IL-21) to activate the suppressed immune system within the tumor microenvironment. Using Salmonella’s flagellar type III secretion system, we engineered the strain to secrete IL-21 directly into the tumor. In a mouse model, we assessed the local immune response and tested the combination of Salmonella-mediated IL-21 delivery with anti-PD-L1 therapy. Our results confirmed IL-21 secretion and showed enhanced recruitment and activation of CD4+ and CD8+ T cells in the tumor. Mice receiving the combination treatment exhibited improved survival and reduced tumor growth compared to monotherapy. Safety studies confirmed the viability of the IL-21-secreting Salmonella strain for therapeutic use. This study highlights Salmonella as a promising platform for cancer immunotherapy. Citation Format: Minju Han, Eunji Kim, Minchan Jeong, Solbi Kim, Heung Jin Jeon, Hyo Jin Lee. Attenuated Salmonella secreting interleukin-21 activates T-cells and induces anti-tumor effects [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B103.