Question ID: WS-64
Submitted by: Esteban Celis
February 22, 2011
The failure of therapeutic cancer vaccines: Who's at fault? How can we expect to observe relevant anti-tumor effects with vaccination strategies that induce meager immune responses? Have we learned little from infectious disease researchers, on how the immune system successfully deals against infectious pathogens? Most cancer vaccines generate less than 1% antigen-specific T cell responses that usually do not persist. On the other hand, during acute viral infections that resolve and generate protective immunity (e.g., influenza, EBV), the proportion of antigen-specific lymphocytes can reach up to 30-60% of all lymphocytes. We keep blaming immune suppressive agents (T-regs, MDSCs) for the failure of current vaccines to elicit strong immune responses and do not consider that the immunogens we use are simply ignored by both innate and adaptive immune systems because they pose little danger. Thus, a successful vaccine will have to mimic an infectious agent to awaken the innate immune system AND at the same time should focus the adaptive immune response towards relevant tumor associated antigens (TAAs). Unfortunately, infectious recombinant viruses expressing TAAs remain suboptimal anti-cancer vaccines because although they stimulate the innate immune system, the adaptive immune system mainly focuses on the viral antigens. One possible solution is to combine the infectious agent's pathogen-associated molecular patterns (e.g., Toll-like receptor agonists) with optimized TAAs to generate meaningful (intense and long-lasting) immune responses that may translate into clinical benefit.
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