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Concurrent OX40 and CD30 Ligand Blockade Abrogates the CD4-Driven Autoimmunity Associated with CTLA4 and PD1 Blockade while Preserving Excellent Anti-CD8 Tumor Immunity
Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.ORCID iD: 0000-0002-9050-0978
Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England..
Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England..
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2017 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 199, no 3, p. 974-981Article in journal (Refereed) Published
Abstract [en]

Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects. In this study, we show that excellent antitumor CD8 T cell responses can be achieved in Foxp3(KO) mice deficient in OX40 and CD30 signals, particularly in the presence of concurrent PD1 blockade. Furthermore, excellent antitumor immune responses can also be achieved using combinations of Abs that block CTLA4, PD1, OX40, and CD30 ligands, without CD4 T cell-driven autoimmunity. By dissociating autoimmune side effects from anticancer immune responses, this potentially shifts this antitumor approach to patients with far less advanced disease.

Place, publisher, year, edition, pages
2017. Vol. 199, no 3, p. 974-981
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-332929DOI: 10.4049/jimmunol.1700088ISI: 000406182600017PubMedID: 28646041OAI: oai:DiVA.org:uu-332929DiVA, id: diva2:1157453
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-01-13Bibliographically approved

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