Prophylactic Vaccine Approach for Colon and Pancreatic Cancers: Present and Future
N. B. Janakiram,
M. S. Bronze,
C. V. Rao.
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.
Keywords: Colon cancer, pancreatic cancer, prophylactic vaccines, tumor-associated antigens, oncoproteins
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