Therapeutic
cancer vaccines aim to generate immunologic targeting of
cancer cells through the induction of effective cellular and antibody-mediated responses specific for
antigens selectively expressed by the
tumor. Exploiting the adaptive immune system as a targeted tool against
cancer is appealing in its capacity for exact specificity and avoidance of unintended tissue damage seen by other conventional agents such as
chemotherapy. There are a multitude of challenges to designing effective
vaccine strategies. The components of a
vaccine strategy start with the challenges of selecting immunogenic,
tumor-specific
antigen targets, choosing a platform with which to deliver the
antigens, and enhancing the immunostimulatory context in which the
vaccines are delivered. Although understanding the components of effective T-cell activation is essential, successful effector T cells can only be produced if there is also an understanding of the natural processes that
tumors exploit to down-modulate active immune responses. These processes are normally used to down-regulate excessive tissue-destructive immune responses against infectious agents once the infecting agent is cleared or to prevent autoimmunity. Advances in molecular and cellular technologies continue to provide insights into the regulation of immune responses both to infectious agents and to
cancer that may be manipulated to tip the balance in favor of
tumor regression over immune tolerance. This review focuses primarily on cellular
vaccines. For the purpose of this review, cellular
vaccines are defined as
vaccines that use whole cells or cell lysates either as the source of
antigens or the platform in which to deliver the
antigens. Dendritic cell (DC)-based
vaccines focus on ex vivo
antigen delivery to DCs. Other platforms such as GVAX (
tumor cells genetically engineered to produce
granulocyte-macrophage colony-stimulating factor) aim to deliver
tumor antigens in vivo in an immune stimulatory context to endogenous DCs. Because data continue to emerge regarding the importance of the maturation status of DCs and the importance of the particular subset of DCs being targeted, these insights will be integrated into
vaccine strategies that are likely to produce more effective
vaccines.