Efficient induction of antitumor immunity by synthetic toll-like receptor ligand-peptide conjugates

• Published in: Cancer immunology research Vol. 2; no. 8; p. 756
• Main Authors: Zom, Gijs G, Khan, Selina, Britten, Cedrik M, Sommandas, Vinod, Camps, Marcel G M, Loof, Nikki M, Budden, Christina F, Meeuwenoord, Nico J, Filippov, Dmitri V, van der Marel, Gijsbert A, Overkleeft, Hermen S, Melief, Cornelis J M, Ossendorp, Ferry
• Format: Journal Article
• Language: English
• Published: United States 01.08.2014
• Subjects: Animals; Cancer Vaccines; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cell Line, Tumor; Dendritic Cells - immunology; Ligands; Lipopeptides - immunology; Lymphoma - pathology; Lymphoma - therapy; Melanoma, Experimental - pathology; Melanoma, Experimental - therapy; Mice, Inbred C57BL; Mice, Transgenic; Toll-Like Receptor 2 - agonists; Toll-Like Receptor 2 - immunology; Tumor Burden
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.cir-13-0223

Chemical conjugates comprising synthetic Toll-like receptor ligands (TLR-L) covalently bound to antigenic synthetic long peptides (SLP) are attractive vaccine modalities, which can induce robust CD8(+) T-cell immune responses. Previously, we have shown that the mechanism underlying the power of TLR-L SLP conjugates is improved delivery of the antigen together with a dendritic cell activation signal. In the present study, we have expanded the approach to tumor-specific CD4(+) as well as CD8(+) T-cell responses and in vivo studies in two nonrelated aggressive tumor models. We show that TLR2-L SLP conjugates have superior mouse CD8(+) and CD4(+) T-cell priming capacity compared with 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.