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Pharm Res. 2002 Jul;19(7):926-32.

Rational design of peptide-based tumor vaccines.

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Division of Pharmaceutical Sciences, Duquesne University, Mylan School of Pharmacy, Pittsburgh, Pennsylvania 15282, USA.


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.

[Indexed for MEDLINE]

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