Concomitant or delayed anti-TNF differentially impact on immune-related adverse events and antitumor efficacy after anti-CD40 therapy.

Journal for Immunotherapy of Cancer
Celia Jacoberger-FoissacMichele W L Teng

Abstract

Concomitant tumor necrosis factor (TNF) neutralization in combination with immune checkpoint inhibitors (ICIs) reduces clinical immune-related adverse events (irAEs) and appears to improve antitumor efficacy in preclinical tumor models. Agonistic antibodies targeting costimulatory receptors such as CD40 represent an additional strategy to boost antitumor immune response and potentiate the activity of ICIs. However, the dose-limiting toxicities observed in anti-CD40-treated cancer patients have hindered its clinical development. We previously described a mouse model to assess both antitumor activity and irAEs induced by various effective combination immunotherapies. Using the BALB/c and C57BL/6 strains of FoxP3-GFP-DTR (FoxP3DTR) mice, transient depletion of T regulatory cells (Tregs) prior to immunotherapy with additional immunomodulatory antibodies, lowered immune self-tolerance, resulting in the development of a spectrum of physical and biochemical irAEs similar to that reported clinically. In MC38 and 4T1.2 tumor models, following transient Treg depletion, we evaluated the impact of anti-CD40 on antitumor efficacy and the development of irAEs and the impact of concomitant or delayed TNF blockade on both these parameters. Phy...Continue Reading

References

Feb 27, 2001·Journal of Immunological Methods·S M TodrykM J Glennie
Oct 16, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kiminori KimuraHisataka Moriwaki
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Silvio DaneseClaudio Fiocchi
Mar 28, 2006·Journal of Leukocyte Biology·Hillary D LumAlexander L Rakhmilevich
Dec 1, 2006·Nature Immunology·Jeong M KimAlexander Y Rudensky
Mar 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert H VonderheideScott J Antonia
Jan 14, 2011·Toxicologic Pathology·Bob ThoolenJerrold M Ward
Mar 11, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marieke F FransenCornelis J M Melief
Jul 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ann L WhiteMartin J Glennie
Jul 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jermaine CowardFrances R Balkwill
Mar 6, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert H Vonderheide, Martin J Glennie
Dec 17, 2014·Clinical & Translational Immunology·Jing LiuMichele Wl Teng
Dec 18, 2014·World Journal of Gastroenterology : WJG·Roberta Elisa RossiCharles Daniel Murray
Dec 23, 2015·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Joshua B FrenchHerbert L Bonkovsky
May 5, 2016·Nature Reviews. Clinical Oncology·Celine BoutrosCaroline Robert
Dec 9, 2016·Expert Review of Anticancer Therapy·Gregory L BeattyKristen B Long
Feb 12, 2017·Cell·Padmanee SharmaAntoni Ribas
Dec 24, 2017·Nature Communications·Florie BertrandBruno Ségui
Jan 11, 2018·British Journal of Cancer·Russell W JenkinsKeith T Flaherty
Mar 24, 2018·Science·Antoni Ribas, Jedd D Wolchok
Aug 12, 2018·Molecular Cancer Therapeutics·Jun IshiharaJeffrey A Hubbell
Sep 2, 2018·Journal of Translational Medicine·Steven F JosephsAmir Jafri
Oct 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·David A KnorrJeffrey V Ravetch
May 6, 2019·Trends in Immunology·Kristen E PaukenArlene H Sharpe
Jan 29, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rik J VerheijdenKarijn P M Suijkerbuijk
Feb 28, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jeffrey S Weber, Michael A Postow
Mar 26, 2020·Cytokine·Pouya Mahdavi SharifNima Rezaei
Apr 5, 2020·Nature Reviews. Clinical Oncology·Khashayar EsfahaniLeonard Calabrese
Jul 1, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J B A G HaanenUNKNOWN ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

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Citations

Feb 6, 2021·Cancers·María Florencia MercoglianoRoxana Schillaci
Mar 15, 2021·Trends in Immunology·Jee Hye KangArabella Young

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Clinical Trials Mentioned

NCT02706353
NCT02665416
NCT02304393

Software Mentioned

Aperio ImageScope
GraphPad Prism

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