Therapeutic
vaccines represent an attractive approach to
cancer treatment. Traditionally,
cancer immunotherapy targets
antigens expressed by the
tumor cells. Although numerous clinical trials studying different
cancer vaccines have been conducted during the past twenty years, very limited clinical responses have been observed. The inefficient anti-
tumor immunity is thought to be due, in major part, to the escape mechanisms exerted by the genetically unstable
tumor cells, e.g., emergence of
antigen-loss mutants, downregulation of MHC molecules and lack of expression of costimulatory molecules. Recently, a novel
vaccine strategy has been developed to circumvent these obstacles. Taking advantage of the importance of angiogenesis in
tumor growth and the genetic stability of endothelial cells, this
immunotherapy strategy targets
antigens (e.g., angiogenic
growth factor receptors) overexpressed by the
tumor neo-vasculature rather than the
tumor cells per se. For example, active immunization against
vascular endothelial growth factor receptor-2 (VEGFR-2) has been shown to generate strong cellular and humoral immune responses, which lead to the inhibition of angiogenesis and
tumor growth and
metastasis. This review provides an outline of this emerging field and discusses the advantages and potential pitfalls of such a
vaccine strategy.