American Association for Cancer Research
23266066cir130223-sup-fig2.pdf (679.18 kB)

Supplementary Figure 2 from Efficient Induction of Antitumor Immunity by Synthetic Toll-like Receptor Ligand–Peptide Conjugates

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journal contribution
posted on 2023-04-03, 23:03 authored by Gijs G. Zom, Selina Khan, Cedrik M. Britten, Vinod Sommandas, Marcel G.M. Camps, Nikki M. Loof, Christina F. Budden, Nico J. Meeuwenoord, Dmitri V. Filippov, Gijsbert A. van der Marel, Hermen S. Overkleeft, Cornelis J.M. Melief, Ferry Ossendorp

PDF file - 679K, Supplementary figure 2. In vitro T-cell activation induced by conjugated SLP.



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. Cancer Immunol Res; 2(8); 756–64. ©2014 AACR.