Isotype switching converts anti-CD40 antagonism to agonism to elicit potent antitumor activity

Accepted/In Press date: 21 April 2020

e-pub ahead of print date: 21 May 2020

Published date: 8 June 2020

Additional Information: Funding Information: We thank the members of the Antibody and Vaccine group for useful discussions and the preclinical unit staff for animal husbandry. We thank Diamond Light Source for beam time on B21 (ref. SM21035-186) and to Nikul Khunti for his support. We thank David Johnston from the Biomedical Imaging Unit, Southampton General Hospital, Southampton, UK, for assistance with Confocal. Funding was provided by Cancer Research UK grants A10834 , A20537 , A18087 , A25139 , and A25169 , as well as European Union FP7 grant 602262-2 . Funding Information: M.S.C. acts as a consultant for a number of biotech companies, being retained as a consultant for BioInvent and has received research funding from BioInvent, GSK, UCB, iTeos, and Roche. M.J.G. acts as a consultant to a number of biotech companies and receives institutional payments and royalties from antibody patents and licenses. This work is related to patent Family WO 2015/145360 protecting antibodies containing modified hIgG2 domains which elicit agonist or antagonistic properties. Funding Information: We thank the members of the Antibody and Vaccine group for useful discussions and the preclinical unit staff for animal husbandry. We thank Diamond Light Source for beam time on B21 (ref. SM21035-186) and to Nikul Khunti for his support. We thank David Johnston from the Biomedical Imaging Unit, Southampton General Hospital, Southampton, UK, for assistance with Confocal. Funding was provided by Cancer Research UK grants A10834, A20537, A18087, A25139, and A25169, as well as European Union FP7 grant 602262-2. X.Y. designed and performed the experiments, analyzed and interpreted data, and wrote the manuscript. H.T.C.C. C.A.P. J.K. H.F. T.I. C.I.M. R.R.F. P.J.D. L.R.D. V.E. J.S.V. A.L.W. and I.T. generated or provided key reagents or performed and analyzed the research. M.J.G. designed the study, supervised data collection, discussed and interpreted data, and edited the manuscript. M.S.C. designed the study, supervised data collection, discussed and interpreted data, and wrote the manuscript with X.Y. M.J.G. and M.S.C. were co-senior authors on the study. M.S.C. acts as a consultant for a number of biotech companies, being retained as a consultant for BioInvent and has received research funding from BioInvent, GSK, UCB, iTeos, and Roche. M.J.G. acts as a consultant to a number of biotech companies and receives institutional payments and royalties from antibody patents and licenses. This work is related to patent Family WO 2015/145360 protecting antibodies containing modified hIgG2 domains which elicit agonist or antagonistic properties. Publisher Copyright: © 2020 The Authors

Keywords: CD40, Fc engineering, TNF receptor, agonists, antagonists, antibody, hIgG2, immunostimulatory, immunotherapy, structure function

Local EPrints ID: 441073

URI: http://eprints.soton.ac.uk/id/eprint/441073

DOI: doi:10.1016/j.ccell.2020.04.013

ISSN: 1535-6108

PURE UUID: a1a6131d-41d0-478f-a9c6-5843adb58b96

ORCID for H. T.Claude Chan: orcid.org/0000-0003-0530-9480

ORCID for Hayden Fisher: orcid.org/0000-0003-0093-0921

ORCID for Patrick J. Duriez: orcid.org/0000-0003-1814-2552

ORCID for Ivo Tews: orcid.org/0000-0002-4704-1139

ORCID for Mark S. Cragg: orcid.org/0000-0003-2077-089X

Date deposited: 29 May 2020 16:30

Last modified: 17 Mar 2024 05:31