Abstract 3243: Modulating the brain immune system to fight cancer in 3 dimensions

Abstract Despite the remarkable efficiency of immune checkpoint modulators against primary and metastatic brain neoplasms, there is a low percentage of responders and clinical trials report severe immune-mediated side effects and disease relapse. An accumulated body of evidence show that non-tumor cells within the tumor microenvironment (TME), specifically the brain microenvironment (BME), including tumor vasculature and immune stromal cells, such as astrocytes, microglia and pericytes, dictate the overall therapeutic efficacy. We synthesized a biodegradable, off-the-shelf and cost-effective nano-sized polymeric platform that combines a cancer vaccine with the targeted inhibition of molecular and/or cellular immune suppressive players. These precision nano-sized medicines aim to re-educate and harness patient T-cell response against tumors, leading to an immunological memory able to control tumor relapse without any follow-up treatment. The design of these advanced peptide and RNA immunotherapeutics is guided by the identification of lead immune suppressor factors and tumor-specific antigens and proinflammatory cytokines using novel 3D bio-printed brain tumor-immune models developed in our lab. Using this unique model platform we identified P-selectin as a novel immune checkpoint in the brain regulating cancer cells-microglia and tumor-associated macrophages interactions. Combining a P-selectin inhibitor with our first nano-immunotherapy candidates sensitized brain malignancies mouse models to immune-checkpoint modulators, dramatically increasing disease-free survival rates. Citation Format: Eilam Yeini, Daniella Vaskovich-Koubi, Ron Kleiner, Helena F. Florindo, Ronit Satchi-Fainaro. Modulating the brain immune system to fight cancer in 3 dimensions [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 3243.