Rational design of peptide-based tumor vaccines.
Administration of synthetic peptides derived from proteins uniquely or overexpressed in tumor cells (tumor-associated antigens) can elicit tumor-specific immune responses in vivo. This is because cytotoxic T lymphocytes can recognize and lyse tumor cells that display peptides derived from tumor-associated antigens (TAAs) in the context of class I major histocompatibility complex (MHC) molecules. TAA peptides, in contrast to peptides of viral origin, generally bind weakly to the MHC molecule. In many cases, this explains the poor magnitude of T cell response directed at the tumor in vivo. Improving MHC binding as a strategy to upregulate antigen recognition can convert low affinity TAA peptides into useful tools in clinical trial settings. High-resolution structures of class I MHC molecules reported over the past two decades provided the framework for designing peptides that can induce optimal T cell response. This review will discuss the basic and clinical aspects of modifying native TAA peptides as tumor vaccines.
Division of Pharmaceutical Sciences, Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania 15282, USA. meng@duq.edu
Wilson S
WS
Meng
Lisa H
LH
Butterfield
D000818:Animals; D019496:Cancer Vaccines / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D022223:Vaccines, Subunit / Q000737:chemistry* / Q000627:therapeutic use
D019496:Cancer Vaccines; D022223:Vaccines, Subunit