Abstract A68: Listeria monocytogenes-based vaccines to mediate targeted ablation of the tumor-associated vasculature in colorectal cancer


 Anti-cancer vaccines are consequential and useful tools in eliciting long-term immune responses against tumor-associated antigens (TAAs). Attenuated listeria monocytogenes represents one such vaccine modality for inducing durable immune-driven responses against MHC class I/II presented antigens. Rather than direct this form of therapy against the dynamic assortment of targets expressed directly by tumor cells, we have instead conjugated listeria-based listeriolysin O (LLO) to RGS5, a critical molecule for cancer angiogenesis. Intriguingly, RGS5 is upregulated by pericytes in nascent blood vessels within the tumor microenvironment, and the destabilization of such blood vessel networks can effectively induce regressions of vascularized tumors like colon cancer. Our initial in vivo studies in mice immunized with the RGS5-LLO vaccine demonstrated significant protection against the aggressive colon cancer line MC38. Such findings provide the rationale for continuing efforts in developing a listeria-based therapeutic regimen against RGS5 and understanding the mechanistic interplay between vaccine-directed immune cells and tumor-derived blood vessels in this model.
 Citation Format: Trevor S Anderson, Amanda L Wooster, Mariam Oladejo, Laurence Wood, Devin Lowe. Listeria monocytogenes-based vaccines to mediate targeted ablation of the tumor-associated vasculature in colorectal 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 A68.