Development of an anti-BAG3 humanized antibody for treatment of pancreatic cancer.
Adaptor Proteins, Signal Transducing
/ antagonists & inhibitors
Animals
Antibodies, Monoclonal, Humanized
/ therapeutic use
Carcinoma, Pancreatic Ductal
/ drug therapy
Cell Line
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Female
Heterografts
Humans
Mice
Pancreatic Neoplasms
/ drug therapy
Pancreatic Neoplasms
BAG3
humanized antibody
pancreatic cancer
pancreatic ductal adenocarcinoma
tumor therapy
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
27
11
2018
revised:
25
03
2019
accepted:
10
04
2019
pubmed:
12
4
2019
medline:
6
5
2020
entrez:
12
4
2019
Statut:
ppublish
Résumé
We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti-BAG3 murine antibody. Here, we used complementarity-determining region (CDR) grafting to generate a humanized version of the anti-BAG3 antibody that may be further developed for possible clinical use. We show that the humanized anti-BAG3 antibody, named BAG3-H2L4, abrogates BAG3 binding to macrophages and subsequent release of IL-6. Furthermore, it specifically localizes into tumor tissues and significantly inhibits the growth of Mia PaCa-2 pancreatic cancer cell xenografts. We propose BAG3-H2L4 antibody as a potential clinical candidate for BAG3-targeted therapy in pancreatic cancer.
Identifiants
pubmed: 30973679
doi: 10.1002/1878-0261.12492
pmc: PMC6547619
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antibodies, Monoclonal, Humanized
0
Banques de données
GENBANK
['NM_004281.3', 'NM_013863.5', 'NP_004272.2']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1388-1399Informations de copyright
© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Références
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7497-502
pubmed: 20368414
Am J Gastroenterol. 2013 Jul;108(7):1178-80
pubmed: 23821002
Oncol Rep. 2016 Mar;35(3):1629-35
pubmed: 26707573
Cell Cycle. 2011 Mar 1;10(5):850-2
pubmed: 21311226
J Clin Endocrinol Metab. 2012 Jan;97(1):E115-20
pubmed: 22072743
J Invest Dermatol. 2012 Jan;132(1):252-4
pubmed: 21850027
Cell Death Dis. 2015 Mar 12;6:e1692
pubmed: 25766331
Am J Pathol. 2011 Jun;178(6):2504-12
pubmed: 21561597
J Biol Chem. 2013 Mar 8;288(10):6980-90
pubmed: 23341456
Cell Death Dis. 2011 Apr 07;2:e141
pubmed: 21472004
Cell Death Dis. 2014 Apr 10;5:e1173
pubmed: 24722298
FEBS Lett. 2003 Apr 24;541(1-3):11-5
pubmed: 12706811
Am J Pathol. 2006 Sep;169(3):761-73
pubmed: 16936253
Transl Oncol. 2013 Dec 01;6(6):676-84
pubmed: 24466370
Semin Cell Dev Biol. 2018 Jun;78:85-92
pubmed: 28864347
Exp Cell Res. 2012 Jan 1;318(1):16-24
pubmed: 22020323
Cell Death Dis. 2011 Mar 31;2:e139
pubmed: 21451574
J Clin Invest. 2017 Aug 1;127(8):3189-3200
pubmed: 28737513
Oncogene. 2012 Dec 13;31(50):5153-61
pubmed: 22310281
Biomed Res Int. 2014;2014:516518
pubmed: 24895585
Ann Surg Oncol. 2015 Dec;22 Suppl 3:S1365-70
pubmed: 25968616
Exp Mol Med. 2002 May 31;34(2):167-71
pubmed: 12085992
Clin Cancer Res. 2019 Jan 15;25(2):892-893
pubmed: 30647085
Oncotarget. 2014 Aug 30;5(16):6846-53
pubmed: 25149536
CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29
pubmed: 25559415
Am J Transl Res. 2015 Dec 15;7(12):2805-14
pubmed: 26885277
Biochim Biophys Acta. 2012 Dec;1826(2):365-9
pubmed: 22710027
Cell Death Dis. 2013 Feb 14;4:e495
pubmed: 23412388
Int J Biochem Cell Biol. 2007;39(7-8):1337-42
pubmed: 17493862
J Am Coll Cardiol. 2017 Apr 4;69(13):1653-1665
pubmed: 28359509
Circ Res. 2010 Nov 12;107(10):1220-31
pubmed: 20884878
JACC Heart Fail. 2014 Dec;2(6):673-5
pubmed: 25262365
Nat Commun. 2015 Nov 02;6:8695
pubmed: 26522614
Oxid Med Cell Longev. 2018 May 31;2018:5967890
pubmed: 29955247
Am J Pathol. 2012 Nov;181(5):1524-9
pubmed: 22944597
Mol Med Rep. 2018 Apr;17(4):5754-5763
pubmed: 29484408
Gut. 2018 Apr;67(4):780-782
pubmed: 28801350
J Clin Invest. 2017 Aug 1;127(8):2900-2903
pubmed: 28737514
J Biol Chem. 1999 Jan 8;274(2):781-6
pubmed: 9873016
J Cell Physiol. 2017 Feb;232(2):309-311
pubmed: 27414463
Gynecol Oncol. 2015 Oct;139(1):30-9
pubmed: 26232338
BMC Cancer. 2018 Aug 6;18(1):793
pubmed: 30081850
Oncotarget. 2017 Jun 30;8(46):80393-80404
pubmed: 29113311
Appl Immunohistochem Mol Morphol. 2013 Dec;21(6):518-24
pubmed: 23455184
Oncotarget. 2016 Jan 5;7(1):700-11
pubmed: 26621836
JCI Insight. 2017 Jul 20;2(14):
pubmed: 28724793
Mol Cancer Ther. 2015 Mar;14(3):642-8
pubmed: 25564440
Cancer Res. 2014 Sep 1;74(17):4731-40
pubmed: 24994713
Anticancer Res. 2017 Apr;37(4):1931-1934
pubmed: 28373462
Chem Commun (Camb). 2018 Jul 5;54(55):7613-7616
pubmed: 29926854