title: A combined approach of human leukocyte antigen ligandomics and immunogenicity analysis to improve peptide-based cancer immunotherapy.
abstract: The breakthrough development of immune checkpoint inhibitors as clinically effective novel therapies demonstrates the potential of cancer immunotherapy. The identification of suitable targets for specific immunotherapy, however, remains a challenging task. Most peptides previously used for vaccination in clinical trials were able to elicit strong immunological responses but failed with regard to clinical benefit. This might, at least partly, be caused by an inadequate peptide selection, usually derived from established tumor-associated antigens which are not necessarily presented as human leukocyte antigen (HLA) ligands. Recently, HLA ligandome analysis revealed cancer-associated peptides, which have been used in clinical trials showing encouraging impact on survival. To improve peptide-based cancer immunotherapy, our group established a combined approach of HLA ligandomics and immunogenicity analysis for the identification of vaccine peptides. This approach is based on the identification of naturally presented HLA ligands on tumor samples, the selection of tumor-associated/tumor-specific HLA ligands and their subsequent testing for immunogenicity in vitro. In this review, we want to present our pipeline for the identification of vaccine peptides, focusing on ovarian cancer, and want to discuss differences to other approaches. Furthermore, we want to give a short outlook of a potential multi-peptide vaccination trial using the novel identified peptides.
authors.affiliation: Department of Immunology, Institute of Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany, janet-peper@gmx.de.
authors.forename: Janet Kerstin
authors.initials: JK
authors.lastname: Peper
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D008024:Ligands; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000378:metabolism; D022223:Vaccines, Subunit
chemical_list: D000951:Antigens, Neoplasm; D006680:HLA Antigens; D008024:Ligands; D010446:Peptide Fragments; D022223:Vaccines, Subunit
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