Sustained Persistence of IL2 Signaling Enhances the Antitumor Effect of Peptide Vaccines through T-cell Expansion and Preventing PD-1 Inhibition.

ABSTRACT: Peptide vaccines can be a successful and cost-effective way of generating T-cell responses against defined tumor antigens, especially when combined with immune adjuvants such as poly-IC. However, strong immune adjuvants can induce a collateral increase in numbers of irrelevant, nonspecific T cells, which limits the effectiveness of the peptide vaccines. Here, we report that providing prolonged IL2 signaling in the form of either IL2/anti-IL2 complexes or pegylated IL2 overcomes the competitive suppressive effect of irrelevant T cells, allowing the preferential expansion of antigen-specific T cells. In addition to increasing the number of tumor-reactive T cells, sustained IL2 enhanced the ability of T cells to resist PD-1-induced negative signals, increasing the therapeutic effectiveness of

SUBMITTER: Sultan H 

PROVIDER: S-EPMC6049806 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature