TY - JOUR
T1 - Optimization of peptide vaccines to induce robust antitumor CD4 T-cell responses
AU - Kumai, Takumi
AU - Lee, Sujin
AU - Cho, Hyun Il
AU - Sultan, Hussein
AU - Kobayashi, Hiroya
AU - Harabuchi, Yasuaki
AU - Celis, Esteban
N1 - Funding Information:
This work was supported by grants R01CA136828 and R01CA157303 from the NCI of the NIH and by start-up funds from Augusta University, Georgia Cancer Center, and the Georgia Research Alliance (GRA).
Publisher Copyright:
© 2016 AACR.
PY - 2017/1
Y1 - 2017/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85016132017&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-16-0194
DO - 10.1158/2326-6066.CIR-16-0194
M3 - Article
C2 - 27941004
AN - SCOPUS:85016132017
SN - 2326-6066
VL - 5
SP - 72
EP - 83
JO - Cancer immunology research
JF - Cancer immunology research
IS - 1
ER -