Imaging Mass Cytometry and Single-Cell Genomics Reveal Differential Depletion and Repletion of B-Cell Populations Following Ofatumumab Treatment in Cynomolgus Monkeys.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2019
Historique:
received: 07 02 2019
accepted: 28 05 2019
entrez: 9 7 2019
pubmed: 10 7 2019
medline: 23 10 2020
Statut: epublish

Résumé

Ofatumumab is the first, fully human, anti-CD20 monoclonal antibody in Phase 3 development for multiple sclerosis (MS). The study focused on changes in lymphocyte subsets in blood and lymphoid tissues and on potential novel biomarkers as a result of anti-CD20 antibody action in Cynomolgus monkeys treated with human equivalent doses of subcutaneous (s.c.) ofatumumab on Days 0, 7, and 14. Axillary lymph nodes (LNs) and blood samples were collected at various time points until Day 90. Lymphocyte subsets were quantified by flow cytometry, while morphological and immune cell changes were assessed by imaging mass cytometry (IMC), immunohistochemistry (IHC), in situ hybridization (ISH), and transcriptome analyses using single-cell methodology. Ofatumumab treatment resulted in a potent and rapid reduction of B cells along with a simultaneous drop in CD20

Identifiants

pubmed: 31281311
doi: 10.3389/fimmu.2019.01340
pmc: PMC6596277
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
ofatumumab M95KG522R0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1340

Références

Rheumatology (Oxford). 2001 Feb;40(2):205-11
pubmed: 11257159
J Exp Med. 2001 Oct 15;194(8):1151-64
pubmed: 11602643
Transpl Immunol. 2003 Oct-Nov;12(1):19-28
pubmed: 14551029
Eur J Immunol. 2004 Dec;34(12):3446-55
pubmed: 15517614
J Immunother. 2005 May-Jun;28(3):212-9
pubmed: 15838377
Am J Pathol. 2006 Feb;168(2):476-89
pubmed: 16436662
J Immunol. 2006 Jul 1;177(1):362-71
pubmed: 16785532
Ann Neurol. 2008 Mar;63(3):395-400
pubmed: 18383069
Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):871-7
pubmed: 18624676
Biotechnol J. 2008 Oct;3(9-10):1157-71
pubmed: 18702090
Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13945-50
pubmed: 19666484
Ann Neurol. 2009 Oct;66(4):460-71
pubmed: 19847908
Arthritis Rheum. 2009 Dec;60(12):3563-71
pubmed: 19950291
Rheumatology (Oxford). 2011 Aug;50(8):1401-8
pubmed: 21398661
Clin Immunol. 2012 Jan;142(1):31-7
pubmed: 21555250
AAPS J. 2012 Sep;14(3):559-70
pubmed: 22619041
J Neuroimmune Pharmacol. 2013 Dec;8(5):1251-64
pubmed: 23821341
PLoS One. 2013 Nov 12;8(11):e80533
pubmed: 24265828
Neurology. 2014 Feb 18;82(7):573-81
pubmed: 24453078
J Immunol. 2014 Jul 15;193(2):580-586
pubmed: 24928997
Toxicol Appl Pharmacol. 2014 Sep 1;279(2):230-9
pubmed: 24937321
Nat Rev Immunol. 2015 Mar;15(3):137-48
pubmed: 25656706
J Virol. 2015 May;89(9):4748-59
pubmed: 25673724
Curr Opin Chem Eng. 2015 Feb 1;7:65-74
pubmed: 25745594
N Engl J Med. 2017 Jan 19;376(3):221-234
pubmed: 28002679
N Engl J Med. 2017 Apr 27;376(17):1694
pubmed: 28445661
Front Immunol. 2018 Feb 26;9:348
pubmed: 29535724
Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):9773-9778
pubmed: 30194232
Brain. 2019 Jan 1;142(1):120-132
pubmed: 30561509
Toxicol Pathol. 2019 Jan;47(1):53-72
pubmed: 30563426
Cells. 2018 Dec 28;8(1):null
pubmed: 30597851
J Immunol. 1980 Oct;125(4):1678-85
pubmed: 6157744

Auteurs

Diethilde Theil (D)

Novartis Pharma AG, Basel, Switzerland.

Paul Smith (P)

Novartis Pharma AG, Basel, Switzerland.

Catherine Huck (C)

Novartis Pharma AG, Basel, Switzerland.

Yoann Gilbart (Y)

Novartis Pharma AG, Basel, Switzerland.

Algirdas Kakarieka (A)

Novartis Pharma AG, Basel, Switzerland.

David Leppert (D)

Neurological Clinic and Policlinic, University Hospital Basel, Basel, Switzerland.

Celine Rauld (C)

Novartis Pharma AG, Basel, Switzerland.

Cindy Schmid (C)

Novartis Pharma AG, Basel, Switzerland.

Reto Baumgartner (R)

Novartis Pharma AG, Basel, Switzerland.

Nathalie Stuber (N)

Novartis Pharma AG, Basel, Switzerland.

Francisco Cordoba (F)

Novartis Pharma AG, Basel, Switzerland.

Valerie Dubost (V)

Novartis Pharma AG, Basel, Switzerland.

Katy Darribat (K)

Novartis Pharma AG, Basel, Switzerland.

Magali Jivkov (M)

Novartis Pharma AG, Basel, Switzerland.

Wilfried Frieauff (W)

Novartis Pharma AG, Basel, Switzerland.

Rainer Kneuer (R)

Novartis Pharma AG, Basel, Switzerland.

Markus Stoeckli (M)

Novartis Pharma AG, Basel, Switzerland.

Stefan Reinker (S)

Novartis Pharma AG, Basel, Switzerland.

Keith Mansfield (K)

Novartis Pharma AG, Basel, Switzerland.

José M Carballido (JM)

Novartis Pharma AG, Basel, Switzerland.

Philippe Couttet (P)

Novartis Pharma AG, Basel, Switzerland.

Gisbert Weckbecker (G)

Novartis Pharma AG, Basel, Switzerland.

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Classifications MeSH