Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma

MAbs
Marije B OverdijkPaul W H I Parren

Abstract

Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA's mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt's lymphoma cell lines. Phagocytosis contributed to DARA's anti-tumor activity in vivo, in both a subcutaneous and an intravenous leukemic xenograft mouse model. Finally, DARA was shown to induce macrophage-mediated phagocytosis of MM cells isolated from 11 of 12 MM patients that showed variable levels of CD38 expression. In summary, we demonstrate that phagocytosis is a fast, potent and clinically relevant mechanism of action that may contribute to the thera...Continue Reading

References

Apr 21, 1988·Nature·A R Duncan, G Winter
Feb 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·E E IdusogieM G Mulkerrin
Apr 3, 2001·The Journal of Experimental Medicine·P A OldenborgF P Lindberg
Oct 7, 2004·Journal of Leukocyte Biology·Joel A Swanson, Adam D Hoppe
Nov 18, 2005·Blood·Shyamsundar SubramanianDennis E Discher
Jul 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tom van MeertenSaskia B Ebeling
Sep 13, 2006·Cancer Metastasis Reviews·Alberto MantovaniAntonio Sica
Oct 3, 2007·Blood·Ezogelin OflazogluHans-Peter Gerber
Nov 6, 2007·Nature Immunology·Katsuto TakenakaJayne S Danska
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marzia LeidiJosée Golay
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tanja Schneider-MerckMichael Dechant
Oct 21, 2010·Annals of the New York Academy of Sciences·Isabelle MartinsGuido Kroemer
Dec 24, 2010·Science Translational Medicine·Mark P ChaoIrving L Weissman
Dec 29, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michel de WeersPaul W H I Parren
Aug 20, 2011·Leukemia·N W C J van de DonkH M Lokhorst
Nov 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Xi Wen ZhaoTimo K van den Berg
Sep 8, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marije B OverdijkPaul W H I Parren
Oct 30, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katharine D GruganRandall J Brezski
Jun 1, 2013·Science·Kipp WeiskopfK Christopher Garcia
Sep 10, 2013·Biophysical Journal·Debjani PaulPietro Cicuta
Nov 2, 2013·The Journal of Clinical Investigation·Fabricio MontalvaoPhilippe Bousso
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jutta DeckertVéronique Blanc

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Citations

Feb 19, 2016·Immunotherapy·Sharmilan ThanendrarajanFrits van Rhee
Sep 17, 2015·Leukemia & Lymphoma·Taimur Sher, Morie A Gertz
Feb 24, 2016·Current Hematologic Malignancy Reports·Hans C LeeJatin J Shah
May 13, 2015·Molecular Immunology·Andrew T HutchinsonRobert L Raison
Jun 25, 2016·Nature Reviews. Cancer·Camilla EngblomMikael J Pittet
Aug 12, 2016·Future Oncology·Wilson I GonsalvesFrancis K Buadi
Aug 25, 2016·The New England Journal of Medicine·Antonio PalumboUNKNOWN CASTOR Investigators
Oct 19, 2016·Case Reports in Oncological Medicine·Muhammad HusnainAmit Agarwal
Oct 6, 2016·The New England Journal of Medicine·Meletios A DimopoulosUNKNOWN POLLUX Investigators
Feb 13, 2016·Immunological Reviews·Niels W C J van de DonkPaul W H I Parren
Jan 25, 2017·Expert Review of Hematology·Annamaria BrioliMarie Von Lilienfeld-Toal
Apr 22, 2017·Cancer Treatment Reviews·Leo RascheFaith E Davies
Apr 8, 2017·Expert Review of Hematology·María J Cejalvo, Javier de la Rubia
Apr 25, 2017·Expert Opinion on Biological Therapy·Cyrille Touzeau, Philippe Moreau
May 12, 2017·Expert Opinion on Drug Safety·María J CejalvoJavier de la Rubia
Apr 5, 2017·Blood·Harold C SullivanSean R Stowell
Jan 4, 2017·Therapeutic Advances in Hematology·Caitlin Costello
Mar 28, 2018·Expert Review of Hematology·Elena ZamagniMichele Cavo
Jan 18, 2018·Antioxidants & Redox Signaling·Tanveer SharifShashi Gujar
Feb 7, 2018·Cancer·Martin KöhlerMonika Engelhardt
Apr 15, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lai Sum LeohManuel L Penichet
Feb 2, 2018·Frontiers in Immunology·Carlos Cuesta-MateosCecilia Muñoz-Calleja
Nov 23, 2017·Frontiers in Immunology·Gianfranco PittariBenedetto Bruno
Oct 21, 2017·Cancer Metastasis Reviews·James J Driscoll, Magen Brailey
Feb 17, 2018·European Journal of Nuclear Medicine and Molecular Imaging·Lei KangWeibo Cai
Aug 7, 2018·British Journal of Haematology·Aneel PaulusTaimur Sher
Nov 6, 2018·Expert Opinion on Biological Therapy·Francesca BonelloFrancesca Gay
Dec 12, 2018·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Homer C AdamsTineke Casneuf
Jan 30, 2019·The Cancer Journal·Raphaël Szalat, Nikhil C Munshi
Feb 16, 2018·Experimental Hematology & Oncology·Saad Z UsmaniA Kate Sasser

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
xenograft
bioluminescence imaging

Software Mentioned

GraphPad Prism
Prism
M3
SPSS
Biospace
PASW Statistics

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