Pathogen‐Mimicking Cancer Vaccine with Self‐Generated dsRNA Potentiates Innate Immunity Against Colon Cancer

Abstract Due to the resistance to immunotherapies is prevalent, exploring universal immune activation strategies are necessary. Pathogenic systems can inherently stimulate the innate immunity and may potentially boost anti‐tumor immune response; however, their safety profile is not optimal. In this study, a pathogen‐mimicking cancer vaccine (DFC‐YM) based on engineered tumor cells is introduced to potentiate innate immunity in colon cancer treatment. By activating viral‐related genes within tumor cells and inducing the transcription of endogenous double‐stranded RNA, DFC‐YM is endowed with virus‐like genome inside. With externally modification with nano‐sized yeast membrane particles (YM), DFC‐YM can simulate the surface structure and immune activation characteristics of microorganisms. Upon administration, this vaccine exhibits pathogen‐like characteristics, capable of recruiting and activating a substantial number of immune cells, particularly neutrophils, dendritic cells, and macrophages, thereby impeding the progression of colon cancer. When further combined with a prostaglandin E2 inhibitor, the pathogen‐mimicking cancer vaccine can further increase CD8 + T lymphocyte populations, demonstrating an enhanced therapeutic efficacy. This innovative strategy presents a new concept for the development of broad‐spectrum immunotherapeutic approaches against colon cancer.