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 both CD8 cytotoxic 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 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 anti-melanoma responses through the enhancement of proliferative and anti-apoptotic activities of CD4 T cells. These results have practical implications in the design of more effective T-cell based immunotherapies.
- Received August 4, 2016.
- Revision received November 14, 2016.
- Accepted November 23, 2016.
- Copyright ©2016, American Association for Cancer Research.