Enhanced efficacy of mesothelin-targeted immunotoxin LMB-100 and anti-PD-1 antibody in patients with mesothelioma and mouse tumor models.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
03
10
2019
revised:
10
02
2020
accepted:
19
05
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
24
6
2021
Statut:
ppublish
Résumé
LMB-100 is an immunotoxin targeting the cell surface protein mesothelin, which is highly expressed in many cancers including mesothelioma. Having observed that patients receiving pembrolizumab off protocol after LMB-100 treatment had increased tumor responses; we characterized these responses and developed animal models to study whether LMB-100 made tumors more responsive to antibodies blocking programmed cell death protein 1 (PD-1). The overall objective tumor response in the 10 patients who received PD-1 inhibitor (pembrolizumab, 9; nivolumab, 1) after progression on LMB-100 was 40%, and the median overall survival was 11.9 months. Of the seven evaluable patients, four had objective tumor responses, including one complete response and three partial responses, and the overall survival for these patients was 39.0+, 27.7, 32.6+, and 13.8 months. When stratified with regard to programmed death ligand 1 (PD-L1) expression, four of five patients with tumor PD-L1 expression had objective tumor response. Patients with positive tumor PD-L1 expression also had increased progression-free survival (11.3 versus 2.1 months,
Identifiants
pubmed: 32611684
pii: 12/550/eaaz7252
doi: 10.1126/scitranslmed.aaz7252
pmc: PMC8499085
mid: NIHMS1740961
pii:
doi:
Substances chimiques
B7-H1 Antigen
0
GPI-Linked Proteins
0
Immunoconjugates
0
Immunotoxins
0
Msln protein, mouse
0
LMB-100
D6AT024T4P
Mesothelin
J27WDC343N
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Intramural NIH HHS
ID : Z01 BC010020
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 BC010816
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 SC007202
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010816
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
Front Med (Lausanne). 2019 Mar 13;6:27
pubmed: 30931305
Toxins (Basel). 2018 Nov 14;10(11):
pubmed: 30441807
Lancet Oncol. 2017 Sep;18(9):1261-1273
pubmed: 28729154
Nat Commun. 2014 Oct 28;5:5241
pubmed: 25348003
J Clin Oncol. 2016 Dec;34(34):4171-4179
pubmed: 27863199
J Clin Invest. 2012 Sep;122(9):3170-83
pubmed: 22850877
J Clin Oncol. 2003 Jul 15;21(14):2636-44
pubmed: 12860938
Immunity. 2018 Jul 17;49(1):178-193.e7
pubmed: 29958801
Int J Cancer. 1992 Jun 19;51(4):548-54
pubmed: 1351045
Front Pharmacol. 2017 Aug 23;8:561
pubmed: 28878676
Cancer Res. 2014 Jun 1;74(11):2907-12
pubmed: 24824231
Clin Immunol. 2008 Nov;129(2):219-29
pubmed: 18771959
Clin Cancer Res. 2016 Mar 1;22(5):1055-8
pubmed: 26463707
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Clin Cancer Res. 2000 Apr;6(4):1476-87
pubmed: 10778980
Lancet. 2016 Apr 2;387(10026):1405-1414
pubmed: 26719230
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Lancet Oncol. 2017 May;18(5):623-630
pubmed: 28291584
J Thorac Oncol. 2018 Oct;13(10):1436-1437
pubmed: 30244849
Lung Cancer. 2014 Jun;84(3):265-70
pubmed: 24321581
Mol Oncol. 2016 Oct;10(8):1317-29
pubmed: 27507537
J Immunother Cancer. 2017 Feb 21;5:18
pubmed: 28239471
Oncologist. 2015 Feb;20(2):176-85
pubmed: 25561510
Cancer Discov. 2016 Feb;6(2):133-46
pubmed: 26503962
BMC Bioinformatics. 2005 Sep 12;6:225
pubmed: 16156896
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Int Immunol. 2015 Jan;27(1):39-46
pubmed: 25323844
Cancer Immunol Res. 2017 Aug;5(8):685-694
pubmed: 28674083
Am J Surg Pathol. 2003 Nov;27(11):1418-28
pubmed: 14576474
J Immunol. 2009 Dec 15;183(12):7898-908
pubmed: 20007574
Front Oncol. 2018 Mar 28;8:86
pubmed: 29644214
JAMA Oncol. 2019 Mar 1;5(3):351-357
pubmed: 30605211
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):136-40
pubmed: 8552591
Clin Cancer Res. 2017 Mar 15;23(6):1564-1574
pubmed: 27635089
Cell Immunol. 2018 Dec;334:38-41
pubmed: 30213644
Adv Immunol. 2016;130:75-93
pubmed: 26923000
Lancet. 2005 Jul 30-Aug 5;366(9483):397-408
pubmed: 16054941
Mol Cancer Ther. 2014 Aug;13(8):2040-9
pubmed: 24928849
Ann Oncol. 2004 Feb;15(2):257-60
pubmed: 14760119