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Cancer Immunol Res. 2018 May;6(5):617-627. doi: 10.1158/2326-6066.CIR-17-0549. Epub 2018 Feb 26.

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

Author information

1
Cancer Immunology, Inflammation and Tolerance Program, Augusta University Georgia Cancer Center, Augusta, Georgia.
2
Department of Pathology, Asahikawa Medical University, Asahikawa, Japan.
3
Department of Otolaryngology, Head and Neck Surgery, Asahikawa Medical University, Asahikawa, Japan.
4
Department of Innovative Research for Diagnosis and Treatment of Head and Neck Cancer, Asahikawa Medical University, Asahikawa, Japan.
5
Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Korea.
6
Cancer Immunology, Inflammation and Tolerance Program, Augusta University Georgia Cancer Center, Augusta, Georgia. ecelis@augusta.edu.
#
Contributed equally

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 the vaccines against established tumors. This vaccination strategy using peptides and sustained IL2 could be taken into the clinic for the treatment of cancer. Cancer Immunol Res; 6(5); 617-27. ©2018 AACR.

PMID:
29483127
PMCID:
PMC6049806
[Available on 2019-05-01]
DOI:
10.1158/2326-6066.CIR-17-0549

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