Insights into Peptide-Based Vaccine Design for Cancer Immunotherapy

• Published in: Current medicinal chemistry Vol. 12; no. 13; pp. 1481 - 1494
• Main Authors: LAZOURA, Eliada, APOSTOLOPOULOS, Vasso
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Schiphol Bentham Science Publishers Ltd 01.01.2005; Bentham Science
• Subjects: Amino acids; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - chemistry; Antigens, Neoplasm - immunology; Bioavailability; Biological and medical sciences; Biological Availability; Cancer Vaccines - administration & dosage; Cancer Vaccines - chemical synthesis; Cancer Vaccines - immunology; Combined treatment; Drug Design; Epitopes - immunology; Humans; Immune response; Immune system; Immunogenicity; Immunotherapy; Major Histocompatibility Complex - immunology; Medical sciences; Neoplasms - therapy; Peptides; Peptides - administration & dosage; Peptides - chemical synthesis; Peptides - immunology; Receptors, Antigen, T-Cell - immunology; Treatment. General aspects; Tumors; Vaccines; Antineoplastic agent; Antigen presentation; Carbohydrate antigen; Biological fixation; T cell receptor; Immune response; Tumor associated antigen; Peptides; Immunotherapy; Major histocompatibility system; Molecular interaction; Vaccine
• ISSN: 0929-8673; 1875-533X
• DOI: 10.2174/0929867054039017

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.