TY - JOUR
T1 - Sustained persistence of il2 signaling enhances the antitumor effect of peptide vaccines through t-cell expansion and preventing pd-1 inhibition
AU - Sultan, Hussein
AU - Kumai, Takumi
AU - Fesenkova, Valentyna I.
AU - Fan, Aaron E.
AU - Wu, Juan
AU - Cho, Hyun II
AU - Kobayashi, Hiroya
AU - Harabuchi, Yasuaki
AU - Celis, Esteban
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
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U2 - 10.1158/2326-6066.CIR-17-0549
DO - 10.1158/2326-6066.CIR-17-0549
M3 - Article
C2 - 29483127
AN - SCOPUS:85047739784
SN - 2326-6066
VL - 6
SP - 617
EP - 627
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 5
ER -