In the vast majority of studies conducted to date, activation of cancer-specific T cell immunity through peptide-based immunization has failed to induce objective tumor regression. This failure is particularly troublesome given that these vaccines often stimulate T cell responses. In this review, we attempt to understand the relative failure of peptide cancer vaccines to achieve clinically meaningful responses. In the first part of the review, we discuss specific hurdles to successful application of synthetic peptide-based vaccines including patient variability and epitope selection. In the second part of this review, we summarize the importance of CD4+ T cell help in peptide-based vaccine strategies and offer a potential strategy to improve peptide-based vaccines through the generation of both HLA class I and class II vaccine specific-immune responses.
Keywords: Cancer, immunotherapy, HLA class, resolvins I, HLA class II, synthetic peptide, tumor antigen, CTL, T helper cell
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