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Sustained Persistence of IL2 Signaling Enhances the Antitumor Effect of Peptide Vaccines through T-cell Expansion and Preventing PD-1 Inhibition.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2018 May; Vol. 6 (5), pp. 617-627. Date of Electronic Publication: 2018 Feb 26. - Publication Year :
- 2018
-
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 .<br /> (©2018 American Association for Cancer Research.)
- Subjects :
- Adjuvants, Immunologic administration & dosage
Animals
Antigens, Neoplasm immunology
Combined Modality Therapy
Cytotoxicity, Immunologic drug effects
Drug Administration Schedule
Drug Synergism
Female
Interleukin-2 pharmacology
Lymphocyte Activation drug effects
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms immunology
Neoplasms pathology
Poly I-C administration & dosage
Programmed Cell Death 1 Receptor antagonists & inhibitors
Programmed Cell Death 1 Receptor immunology
Rats
Signal Transduction drug effects
T-Lymphocytes physiology
Tumor Cells, Cultured
Vaccines, Subunit therapeutic use
Cancer Vaccines therapeutic use
Cell Proliferation drug effects
Immunotherapy, Adoptive methods
Interleukin-2 administration & dosage
Neoplasms therapy
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 6
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 29483127
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-17-0549