Optimization of Peptide Vaccines to Induce Robust Antitumor CD4 T-cell Responses

• Type of Material: Article
• Authors: Takumi Kumai, Augusta University; Sujin Lee, Emory University; Hyun-II Cho, Catholic University of Korea; Hussein Sultan, Augusta University; Hiroya Kobayashi, Asahikawa Medical University; Yasuaki Harabuchi, Asahikawa Medical University; Esteban Celis, Augusta University
• Language: English
• Date: 2017-01-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2016 American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/2326-6066.CIR-16-0194
• Title of Journal or Parent Work: Cancer Immunology Research
• ISSN: 2326-6066
• Volume: 5
• Issue: 1
• Start Page: 72
• End Page: 83
• Grant/Funding Information: This work was supported by grants R01CA136828 and R01CA157303 from the National Cancer Institute of the National Institutes of Health and by start-up funds from Augusta University, Georgia Cancer Center, and the Georgia Research Alliance (GRA).
• Keywords: VACCINATION; IMMUNOTHERAPY; DENDRITIC CELLS; VIVO EXPANSION; Science & Technology; IN-VIVO; TUMOR-REGRESSION; OX40; Immunology; Life Sciences & Biomedicine; IMMUNE-RESPONSES; LIGAND INTERACTION; ANTIGEN; Oncology
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Substantial evidence indicates that immunotherapy is a feasible and effective approach for the treatment of numerous types of cancer. Among various immunotherapy options, peptide vaccines to generate antitumor T cells appear as promising candidates, because of their cost effectiveness and ease of implementation. Nevertheless, most peptide vaccines are notorious for being weekly immunogenic and, thus, optimization of the vaccination strategy is essential to achieve therapeutic effectiveness. In addition, effective peptide vaccines must stimulate bothCD8cytotoxic and CD4 helper T lymphocytes. Our group has been successful in designing effective peptide vaccination strategies for inducing CD8 T-cell responses in mouse tumor models. Here, we describe a somewhat similar, but distinct, peptide vaccination strategy capable of generating vast CD4 T-cell responses by combining synthetic peptides with toll-like receptor (TLR) agonists and OX40/CD40 costimulation. This vaccination strategy was efficient in overcoming immune tolerance to a self-tumor-associated antigen and generated significant antitumor effects in a mouse model of malignant melanoma. The optimized peptide vaccine also allowed the expansion of adoptively transferred CD4 T cells without the need for lymphodepletion and IL2 administration, generating effective antimelanoma responses through the enhancement of proliferative and antiapoptotic activities of CD4 T cells. These results have practical implications in the design of more effective T-cell-based immunotherapies.