Enhancement of tumor antigen-specific T cell responses by engineered antigen-presenting cells 3881

Abstract Description Despite their promise, the efficacy of immunotherapies for cancers has been limited. Several factors, including T cell exhaustion, inefficient T cell infiltration, heterogeneity of tumor antigens, and dysfunction of antigen-specific T cells, reduce efficacy. Here, we propose a novel approach to enhance anti-tumor T cell responses by engineering antigen-presenting cells (APCs). Our lab has previously developed chimeric receptors called Signaling and Antigen-presenting Bifunctional receptors (SABRs), which can present a given antigen to T cells and then generate a functional response that can alter the activity of that T cell. Here, we modified SABRs to incorporate signaling domains that can induce intracellular signals in professional APCs. We constructed SABRs presenting Ovalbumin (OVA) peptides in mouse class I and II MHC and encoding for FcgR-CD3z signaling domains. We showed that primary murine monocyte-derived dendritic cells and macrophages engineered to express these SABRs presented OVA peptides to OT-I or OT-IIT cells. Using dye dilution assays, we showed that SABR-expressing APCs enhanced T cell proliferation in vitro, compared to un-modified APCs or APCs expressing pMHC without signaling domains. We are currently performing experiments to test whether SABR-APCs can enhance tumor clearance by OVA-specific T cells in a B16-OVA melanoma model in vivo. Our study will pave the way for novel approaches to improve the efficacy of antigen-specific immunotherapies for cancer Funding Sources Supported by NIH/National Institute of Allergy and Infectious Diseases 1DP2AI176138-01 Topic Categories Antigen and Dendritic Cell Processing, Presentation, and Biology (AGDC)