Chemical conjugates comprising synthetic Toll-like receptor ligands (TLR-L) covalently bound to synthetic antigenic long peptides (SLP) are attractive vaccine modalities which can induce robust CD8+ T cell immune responses. We have previously shown that the mechanism underlying the power of TLR-L SLP-conjugates is improved delivery of the antigen together with a dendritic cell (DC) activation signal. In the present study we now expanded the approach to tumor-specific CD4+ as well as CD8+ T cell-responses and in vivo studies in two non-related aggressive tumor models. We show that TLR2-L SLP conjugates have superior mouse CD8+ and CD4+ T cell priming capacity compared to free SLPs injected together with a free TLR2-L. Vaccination with TLR2-L SLP conjugates leads to efficient induction of antitumor immunity in mice challenged with aggressive transplantable melanoma or lymphoma. Our data indicate that TLR2-L SLP conjugates are suitable to promote integrated antigen-specific CD8+ and CD4+ T cell responses required for the antitumor effects. Collectively, these data show that TLR2-L SLP conjugates are promising synthetic vaccine candidates for active immunotherapy against cancer.
- Received December 13, 2013.
- Revision received February 28, 2014.
- Accepted April 11, 2014.
- Copyright © 2014, American Association for Cancer Research.