The identification of tumour-associated
antigens has opened up new approaches to
cancer immunotherapy. While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against
cancer. In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour
antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in
cancer immunotherapy. The cloning of MHC class I- or class II-associated
antigens has made it possible to develop synthetic and recombinant
cancer vaccines that express specific tumour
antigens. There are three major types of synthetic and recombinant
cancer vaccines: recombinant viral and
bacterial vaccines; naked
DNA or
RNA vaccines; and
recombinant protein and
peptide vaccines. In this article, we also discuss a new generation of recombinant
cancer vaccines, 'self-replicating'
DNA and
RNA vaccines. Studies on the mechanisms of 'self-replicating'
nucleic acid vaccines revealed that the enhanced immunogenicity was not due to an enhanced
antigen expression, suggesting that the quantitative difference may not be as important as the qualitative difference in antigen presentation. The presence of the
RNA replicase in the 'self-replicating'
nucleic acid vaccines mimics
alphavirus infection, which triggers the innate
antiviral pathways of the host cells. Studies on how viral and cellular modulators of the innate
antiviral pathways affect
vaccine function should provide molecular insights crucial to future
vaccine design.