T cell targeted immune enhancement yields effective T cell adjuvants

Given the critical role of cell-mediated immunity (CMI) in defense against attack from pathogens that establish chronic infections, it has become abundantly clear that current vaccine methodology will not be sufficient to develop the appropriate immune response for protection and/or clearance of infection. By extension, this logic also applies to cancer vaccines where T cell immune-mediated destruction is a critical mechanism for control of the disease. This review describes our current thoughts on the events associated with immune activation and evaluates the various approaches to achieve successful immune activation with defined or targeted antigens as opposed to using inactivated or attenuated organisms. The advantages and disadvantages of the current adjuvants for antigens that focus on mimicking the infection events via the innate immune system or antigen uptake are described in the context of generation of T cell specific responses. A central theme of the discussions is the importance of cytokines in modulating the immune response towards T cell immunity, either by adjuvant modulation or use of natural cytokine mixtures targeted towards the site of immune activation. Also discussed is the possibility that thymomimetic agents such as thymosin alpha1, levamisole and methyl inosine monophosphate (MIMP) may be useful in enhancing the T cell mediated arm of the immune response.