Vaccines against
cancers have not been as effective as
vaccines against
infectious diseases. However, recent studies have advanced our understanding of the stages of
tumor cell development and of mechanisms of immune surveillance, immune suppression, and of tumor escape from the immune system. The development of animal models that mimic development of human
cancers has helped advance the understanding of these processes and is aiding the development of greatly improved
vaccines. Here we review the recent progress in developing
vaccines and prophylactic approaches for pancreatic and
colon cancers. Improved understanding of the expression of various oncogenes and
tumor-associated
antigens helps in selecting antigenic targets for stage-specific immune prevention. Identification of the earliest alterations in precancerous lesions and selection of
epitopes unique to the aberrant cells and capable of triggering strong cytotoxic and helper T cell responses may aid the development of safe and effective
vaccines for use in those at high risk of progressing to invasive
cancers. The responses can be enhanced with carefully selected adjuvants to boost immunity and by selecting
epitopes that are expressed on dendritic cells, thereby promoting T cell responses.
Tumor resistance via loss of the targeted
antigen can be mitigated by inclusion of multiple
tumor epitopes in
vaccine constructs. Tumor immune escape can be diminished by targeting various immunosuppressive mechanisms used by different
tumors, such as
tumor production of immunosuppressive
cytokines (e.g.,
interleukin 10, and
Transforming Growth Factor-beta, which can promote activity of immunosuppressive regulatory T cells), or by inhibiting production of inflammatory
prostanoids with combined
cyclooxygenase/
lipoxygenase inhibitors. Finally, prevention of many
cancers may be enhanced by carefully selecting and scheduling of
vaccine administration in combination with other chemotherapeutic or chemopreventive agents. Preclinical and early clinical trials incorporating these principles are discussed.