Vaccination against endothelial cells (ECs) lining the tumor vasculature represents one of the most attractive potential cancer immunotherapy options due to its ability to prevent solid tumor growth. Using this approach, target antigens can be derived from ECs and used to develop a universal cancer vaccine. Unfortunately, direct immunization with EC preparations can elicit autoimmune vasculitis in normal tissues. Recently, tumor-induced changes to the human EC surface were described that provided a basis for designing efficient EC-based vaccines capable of eliciting immune responses that targeted the tumor endothelium directly. This review examines these data from the perspective of designing EC-based cancer vaccines for the treatment of all solid tumors, including the antigen composition of vaccine formulations, the selection ECs for antigen derivation, the production and control of antigens, and the method for estimating vaccine efficacy and safety. As the vaccine preparation requires a specifically derived set of natural cell surface antigens, a new vaccine preparation concept was formulated. Antigen compositions prepared according to this concept were named SANTAVAC (Set of All Natural Target Antigens for Vaccination Against Cancer).
Keywords: HMEC, human microvascular endothelial cells; UCV, universal cancer vaccine; CTA, cytotoxicity assay; CPF, cell proteomic footprinting; CTL, cytotoxic T lymphocytes; SANTAVAC, Set of All Natural Target Antigens for Vaccination Against Cancer; antiangiogenic cancer vaccine; cell heterogeneity; cell proteomic footprinting; cell surface antigens; cell surface profiling; microvascular endothelial cells; universal cancer vaccine; vaccine design.