Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses.

Journal for Immunotherapy of Cancer
Souvik DeyAlexander J Muller

Abstract

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner. CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2d BALB/c strain, were emulsified in 50% Montanide for prophylactic or therapeutic vaccine treatment of CT26 tumor-bearing mice initiated either 7 days prior to or following tumor cell injection, respectively. In some therapeutic treatment experiments, administration of programmed cell death protein 1-binding antibody (anti-PD1 antibody) or epacadostat was concurrently initiated. Tumor size was dete...Continue Reading

References

Jan 1, 1995·Immunogenetics·H G RammenseeS Stevanoviíc
Aug 15, 2002·Human Immunology·Pedro A RecheEllis L Reinherz
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ursula GrohmannPaolo Puccetti
Sep 2, 2004·Nature Medicine·Steven A RosenbergNicholas P Restifo
Oct 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alexander J MullerAndrew L Mellor
May 30, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Alexander M M Eggermont
Feb 18, 2010·Cancer Research·Alexander J MullerGeorge C Prendergast
May 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Burles A JohnsonAndrew L Mellor
Nov 17, 2010·Blood·Rikke Baek SørensenMads Hald Andersen
Jul 24, 2012·Cancer Discovery·Courtney SmithAlexander J Muller
Oct 30, 2012·Trends in Immunology·David H Munn, Andrew L Mellor
Jun 12, 2013·The Journal of Experimental Medicine·Rikke B HolmgaardJames P Allison
Nov 13, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Trine Zeeberg IversenInge Marie Svane
Apr 9, 2014·Cancer Immunology, Immunotherapy : CII·George C PrendergastAlexander J Muller
Jun 13, 2015·Journal of the National Cancer Institute·Mads Hald Andersen
Feb 4, 2016·Trends in Immunology·David H Munn, Andrew L Mellor
Feb 25, 2017·Nature Reviews. Cancer·Mark YarchoanElizabeth M Jaffee
Apr 5, 2017·Journal of the National Cancer Institute·James L GulleyCharles G Drake
Oct 24, 2017·Stem Cell Investigation·Nikolaj Juul NitschkeInge Marie Svane
May 17, 2018·Chinese Clinical Oncology·Ayako Wakatsuki PedersenMai-Britt Zocca
Jul 4, 2018·Seminars in Immunopathology·Mads Hald Andersen
Aug 18, 2018·Cancer Discovery·Spencer C WeiJames P Allison
Sep 12, 2018·Seminars in Immunopathology·Alexander J MullerGeorge C Prendergast

❮ Previous
Next ❯

Citations

Oct 31, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jessica JouEzra E W Cohen
Sep 15, 2021·Cancer Immunology Research·Mia Aaboe JørgensenMads Hald Andersen
Nov 5, 2021·Current Oncology Reports·Alfredo AddeoChristian Rolfo

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
fluorescence-activated cell sorting
flow cytometry

Clinical Trials Mentioned

NCT03562871
NCT02752074
NCT03047928

Software Mentioned

TumGrowth
GenScript

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.