Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Accepted/In Press date: 24 March 2022

e-pub ahead of print date: 4 May 2022

Published date: 26 May 2022

Additional Information: Funding Information: G.F. is an employee of Amgen Inc. B.V. is a consultant for iOnctura (Geneva, Switzerland), Venthera (Palo Alto, US) and Olema Pharmaceuticals (San Francisco, US) and has received speaker fees from Gilead (Foster City, US). K.O. has received consultancy fees from iOnctura, Macomics, Gilead Sciences and Karus Therapeutics and has received research funding from GSK. M.K. is on the scientific advisory board of Prometheus. C.H.O. led the clinical trial of AMG319 with funding by Cancer Research UK, Amgen provided clinical grade compound free of charge for this trial. All other authors declare no conflicts of interest. Funding Information: We thank C. Rommel, K. Ali, P. Johnson and D. Scott for support and help during the initial phases of setting up the CRUK/Amgen collaboration; F. Martin for project support over the years; M. Lopez and the research pathology core at University Hospital Southampton for performing the immunohistochemistry on the paraffin embedded material; I. Henderson for help with the tetanus ELISAs; the La Jolla Institute (LJI) Flow Cytometry Core for assisting with cell sorting; the LJI sequencing core for the bulk and single-cell sequencing; the LJI histology core for processing the mouse histology samples; G. Means for method and training for the phospho-AKT assays; P. Friedmann for constructive critique of the paper; and D. Singh for advice on and help with experimental work. This clinical trial work was funded by a CDD trial Grant CRUKD/15/004 (C.H.O.), a Cancer Research UK Centres Network Accelerator Award Grant (A21998) (O.W., K.M. and J.T.), the CRUK and NIHR Experimental Cancer Medicine Center (ECMC) Southampton (A15581), the CRUK and NIHR ECMC Liverpool (A25153), Cancer Research UK Programme Grant (C23338/A25722 (E.L.-G. and B.V.)); the UK NIHR UCLH Biomedical Research Centre (B.V.), S10OD025052 (Illumina Novaseq6000), S10RR027366 (FACSAria II cell sorter), NIH grant P01 DK46763 (M.K.), the William K. Bowes Jr Foundation (P.V.), Whittaker iCure Foundation (P.V., L.C. and C.H.O.), the Deutsche Forschungsgemeinschaft DFG research fellowship no. WI 5255/1-1:1 (A.v.W.) and Erwin Schrödinger Fellowship (M.D.). The clinical delivery of this work was supported by the Wessex Clinical Research Network and National Institute of Health Research UK. We further acknowledge Cancer Research UK (Centre for Drug Development) as the clinical trial Sponsor and for funding and management of the Phase II clinical trial, as well as Amgen for supply of the PI3Kδi AMG319. Funding Information: We thank C. Rommel, K. Ali, P. Johnson and D. Scott for support and help during the initial phases of setting up the CRUK/Amgen collaboration; F. Martin for project support over the years; M. Lopez and the research pathology core at University Hospital Southampton for performing the immunohistochemistry on the paraffin embedded material; I. Henderson for help with the tetanus ELISAs; the La Jolla Institute (LJI) Flow Cytometry Core for assisting with cell sorting; the LJI sequencing core for the bulk and single-cell sequencing; the LJI histology core for processing the mouse histology samples; G. Means for method and training for the phospho-AKT assays; P. Friedmann for constructive critique of the paper; and D. Singh for advice on and help with experimental work. This clinical trial work was funded by a CDD trial Grant CRUKD/15/004 (C.H.O.), a Cancer Research UK Centres Network Accelerator Award Grant (A21998) (O.W., K.M. and J.T.), the CRUK and NIHR Experimental Cancer Medicine Center (ECMC) Southampton (A15581), the CRUK and NIHR ECMC Liverpool (A25153), Cancer Research UK Programme Grant (C23338/A25722 (E.L.-G. and B.V.)); the UK NIHR UCLH Biomedical Research Centre (B.V.), S10OD025052 (Illumina Novaseq6000), S10RR027366 (FACSAria II cell sorter), NIH grant P01 DK46763 (M.K.), the William K. Bowes Jr Foundation (P.V.), Whittaker iCure Foundation (P.V., L.C. and C.H.O.), the Deutsche Forschungsgemeinschaft DFG research fellowship no. WI 5255/1-1:1 (A.v.W.) and Erwin Schrödinger Fellowship (M.D.). The clinical delivery of this work was supported by the Wessex Clinical Research Network and National Institute of Health Research UK. We further acknowledge Cancer Research UK (Centre for Drug Development) as the clinical trial Sponsor and for funding and management of the Phase II clinical trial, as well as Amgen for supply of the PI3Kδi AMG319. Publisher Copyright: © 2022, The Author(s).

Related URLs:

• https://www.nature.com/article...22-04685-2

Local EPrints ID: 468648

URI: http://eprints.soton.ac.uk/id/eprint/468648

DOI: doi:10.1038/s41586-022-04685-2

ISSN: 0028-0836

PURE UUID: 70d2556e-081a-4aa5-86ae-45232c985b23

Date deposited: 19 Aug 2022 16:38

Last modified: 16 Mar 2024 21:46