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.
Meng
Wilson S
WS
Division of Pharmaceutical Sciences, Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania 15282, USA. meng@duq.edu
Butterfield
Lisa H
LH
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