Sustained persistence of il2 signaling enhances the antitumor effect of peptide vaccines through t-cell expansion and preventing pd-1 inhibition

Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Aaron E. Fan, Juan Wu, Hyun II Cho, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)617-627
Number of pages11
JournalCancer Immunology Research
Volume6
Issue number5
DOIs
StatePublished - May 1 2018

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Subunit Vaccines
Interleukin-2
T-Lymphocytes
Neoplasms
Neoplasm Antigens
Vaccination
Vaccines
Antigens
Costs and Cost Analysis
Peptides
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Sustained persistence of il2 signaling enhances the antitumor effect of peptide vaccines through t-cell expansion and preventing pd-1 inhibition. / Sultan, Hussein; Kumai, Takumi; Fesenkova, Valentyna; Fan, Aaron E.; Wu, Juan; Cho, Hyun II; Kobayashi, Hiroya; Harabuchi, Yasuaki; Celis, Esteban.

In: Cancer Immunology Research, Vol. 6, No. 5, 01.05.2018, p. 617-627.

Research output: Contribution to journalArticle

Sultan, Hussein ; Kumai, Takumi ; Fesenkova, Valentyna ; Fan, Aaron E. ; Wu, Juan ; Cho, Hyun II ; Kobayashi, Hiroya ; Harabuchi, Yasuaki ; Celis, Esteban. / Sustained persistence of il2 signaling enhances the antitumor effect of peptide vaccines through t-cell expansion and preventing pd-1 inhibition. In: Cancer Immunology Research. 2018 ; Vol. 6, No. 5. pp. 617-627.
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AU - Wu, Juan

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