Design of Peptide-Based Vaccines for Cancer

Abstract

The immune system responds efficiently to bacteria, viruses and other agents however, the immune response to cancers is not as effective. In most cases other than specific genetic rearrangements leading to non-self proteins such as in leukemia and idiotypes in lymphoma, tumor associated proteins are self proteins and are not recognized by the immune system to prevent malignancy. In most cancers, patients develop antibodies and/or CTL-precursors to tumor associated antigens but are not effective in generating a therapeutic immune response. Adjuvants have been used with either whole tumors, subunits or peptides with the aim of increasing their immunity. Whole tumor antigens have certain advantages associated with it, such as ready availability as recombinant proteins, potential epitopes that can be presented by a number of MHC class I/II alleles and antibody development. The methods of identification of CD8 and CD4 epitopes either by use of epitope prediction algorithms or use of transgenic mice has made the use of defined synthetic peptides more attractive. The possibility to synthesize long peptides and introduce multiple epitopes (CD4 or CD8) from single or multiple antigens makes peptide a viable alternative to whole proteins. As an alternative to totally synthetic peptide constructs or polymers, polytopes have been generated by genetic engineering methods. In addition, to deliver immunogens to and to activate DC, receptor-mediated delivery of peptides using antibodies, cytokines and carbohydrates have been used. This review will encompass the various strategies, preclinical and clinical applications in designing peptide-based vaccines for cancer.

Towards a Self‐Adjuvanting Multivalent B and T cell Epitope Containing Synthetic Glycolipopeptide Cancer Vaccine

“…In addition, it was established that priming and sustaining of both Ab and CD8 + cytotoxic T cell (CTL) responses, the latter also crucial in cancer immunity, requires CD4 + Th cell help. [5] This suggests that an ideal cancer vaccine formulation must incorporate B cell, CD4 + , and CD8 + T cell epitopes to ensure both humoral and cellular eradication of tumors. [6] Finally, these synthetic multivalent vaccines should be delivered together with potent and safe external immunoadjuvants to ensure an early and strong immunity.…”

“…[7] However, except for a few studies reporting the synthesis of up to three-component multivalent or "polytope" vaccines, [5,8] no molecular constructions have been designed so far on the basis of these overall structural features. This is presumably because of inherent difficulties, [9] despite recent progresses in the synthesis, assembly, and formulation of oligosaccharide and glycoconjugate biomolecules.…”

Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

“…Although therapy including combinations of standard therapy (chemotherapy, radiotherapy, and resection) have been tried, novel strategies for treatment of esophageal cancer are required to improve poor prognosis. Immunotherapy is now developing into a promising and potent strategy, and the clinical benefit of vaccine therapy has recently been reported for treatment of a variety of carcinomas [5,6]. Thus, identification of a useful epitope peptide derived from tumorassociated antigen (TAA) expressed in esophageal cancer could lead to the development of effective vaccine therapy to prolong the survival of patients.…”

MHC and MHC‑like molecules: Structural perspectives on the design of molecular vaccines

“…1). [7][8][9][10][11][12] A long groove between the helices constitutes the binding site for processed peptides. 6 The side chains of peptides, i.e., anchor residues, fit into specificity pockets that extend along the floor of the groove.…”