Endogenous living adjuvants for cancer vaccination: Concepts, mechanisms, and design principles

Cancer vaccination requires effective integration of antigen delivery and immune activation across secondary lymphoid organs and tumor tissues, yet many conventional adjuvants rely on static molecular or material-based cues that are poorly aligned with dynamic antitumor immune processes. To address this gap, the concept of living adjuvants has emerged to describe biologically active systems that enhance vaccination by actively participating in immune regulation rather than serving as passive stimulatory components. While the broader concept may include microorganisms, we focus exclusively on endogenous living adjuvants, defined as self-derived cellular systems, including dendritic cells, red blood cells, B cells, mesenchymal stromal cells, and tumor cells, which share key features such as physiological trafficking, sustained cellular interactions, and amenability to chemical or genetic engineering, enabling integrated immune modulation within a single platform. We define the core concepts and mechanisms underlying endogenous living adjuvants, summarize representative strategies, and discuss design principles that govern their effectiveness, controllability, safety, and translational potential. This review provides a unified framework to guide the rational engineering of endogenous living adjuvants, ultimately informing the development of next-generation cancer immunotherapies.