Abstract A43: Analysis of the effects of therapeutic vaccination with tumor vascular-primed dendritic cells in a mouse model of colon cancer


 Colorectal cancer remains the third leading cause of cancer-related death in the United States despite advances in targeted therapies such as monoclonal antibodies and tyrosine kinase inhibitors. Progression of vascularized tumors, including colorectal cancer, is reliant on a functioning blood system that provides cancer cells sufficient nutrients and oxygen. This process is ultimately driven by a concerted effort of pro-angiogenic factors, namely vascular endothelial growth factors (VEGFs) and their cognate receptors – the VEGF receptors (VEGFRs). However, tumor vascularization tends to be an unregulated process that results in the overexpression of angiogenic molecules that promote the development of abnormal and chaotic blood vessels, which ultimately impede the perfusion and efficacy of small molecule drugs or immune-based approaches that incorporate cytotoxic CD8+ T cells. FDA-approved targeted agents have been developed against major angiogenic components such as VEGF and VEGFRs, but, despite short-term clinical benefits, these drugs are generally cytostatic and quickly lead to resistance in most patients. To address such shortcomings, active immunotherapeutic strategies directed at auxiliary targets within the tumor vasculature represent a potentially improved direction toward prolonging cancer protection by instituting the long-term destruction of endothelial cell and pericyte networks that provide tumors critical support. We hypothesize that therapeutic vaccination using autologous alpha-type-1 polarized dendritic cells (DCs) pulsed with endothelial cell-and pericyte-derived peptides will induce a protective and safe cytotoxic T cell response in animals. This clinically-relevant DC approach should ultimately lead to colon cancer regressions in mice and allow our group to identify immunologic-based mechanisms that contribute to lasting immunity against the disease.
 Citation Format: Amanda L Wooster, Trevor S Anderson, Savanna L Piersall, Devin B Lowe. Analysis of the effects of therapeutic vaccination with tumor vascular-primed dendritic cells in a mouse model of colon cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A43.