Insights into Peptide-Based Vaccine Design for Cancer Immunotherapy

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Abstract:

The presentation of peptides derived from tumor associated proteins (TAAs) by the major histocompatibility complex (MHC) to T cell receptor (TcR) initiates a cascade of events that constitute the immune response. Eliciting an effective immune response, however, requires the coordinated regulation of both the cellular and humoral arms of the immune system. The design of effective peptide-based vaccines for cancer immunotherapeutic applications, therefore, requires intimate knowledge and understanding of peptide-MHC (pMHC) as well as TcR-pMHC interactions. Despite the wealth of information available to date from X-ray crystallographic and biological studies, the task of rationally designing peptide-based vaccines that can effectively prevent and/or treat cancer cell proliferation remains challenging. The complexity of interactions involved are not readily predictable and are further complicated by the involvement of surrounding molecules in vivo, which can lead to reduced biological activity and/or unwanted side effects. Furthermore, the delivery of peptide-based vaccines into the cell, for further processing and presentation to effector cell, represents an additional challenge which needs to be addressed. The incorporation of appropriate chemical entities into peptide-based vaccines can improve cellular uptake thereby enhancing biological activity. Finally, the susceptibility of peptide-based vaccines to enzymatic degradation warrants the need for the incorporation of non-natural amino acids, retro-inversion and/or cyclization to improve bioavailability essentially reducing the required dosage with minimum side effects.





Keywords: dendritic cells (dcs); immunotherapeutics; t cell receptor (tcr); t lymphocytes

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/0929867054039017

Affiliations: Austin Research Institute, Immunology and Vaccine Laboratory, Studley Road, Heidelberg, VIC 3084, Australia.

Publication date: June 1, 2005

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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