Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma 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:
08 02 2023
08 02 2023
Historique:
entrez:
8
2
2023
pubmed:
9
2
2023
medline:
11
2
2023
Statut:
ppublish
Résumé
D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized that immunosuppression in glioblastoma limits D2C7-IT efficacy. To improve the response rate and reverse immunosuppression, we combined D2C7-IT tumor cell killing with αCD40 costimulation of antigen-presenting cells. In murine glioma models, a single intratumoral injection of D2C7-IT+αCD40 treatment activated a proinflammatory phenotype in microglia and macrophages, promoted long-term tumor-specific CD8
Identifiants
pubmed: 36753564
doi: 10.1126/scitranslmed.abn5649
pmc: PMC10440725
mid: NIHMS1923415
doi:
Substances chimiques
Immunotoxins
0
ErbB Receptors
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT04547777']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabn5649Subventions
Organisme : NCI NIH HHS
ID : K08 CA248966
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS119183
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197264
Pays : United States
Références
J Leukoc Biol. 2000 Jan;67(1):2-17
pubmed: 10647992
J Immunol. 2006 Feb 1;176(3):1402-10
pubmed: 16424167
Circulation. 2005 Apr 5;111(13):1690-6
pubmed: 15795333
Cell. 2013 Oct 10;155(2):462-77
pubmed: 24120142
J Neuroimmunol. 2010 May;222(1-2):62-9
pubmed: 20303602
Nat Commun. 2021 Jun 8;12(1):3424
pubmed: 34103524
Clin Cancer Res. 2013 Sep 1;19(17):4717-27
pubmed: 23857604
Cancer Treat Rev. 2019 Nov;80:101896
pubmed: 31541850
Nat Med. 1999 May;5(5):548-53
pubmed: 10229232
Cancer Immunol Immunother. 2008 Aug;57(8):1151-60
pubmed: 18214476
Expert Rev Anticancer Ther. 2017 Feb;17(2):175-186
pubmed: 27927088
Nat Immunol. 2009 Jan;10(1):29-37
pubmed: 19043418
Science. 2011 Mar 25;331(6024):1612-6
pubmed: 21436454
Front Immunol. 2019 Jun 11;10:1315
pubmed: 31244854
Cancer Res. 2016 Nov 1;76(21):6266-6277
pubmed: 27634762
World Neurosurg. 2019 Oct;130:e17-e25
pubmed: 31125770
Sci Rep. 2016 Feb 10;6:20686
pubmed: 26861911
Clin Cancer Res. 2018 Sep 1;24(17):4175-4186
pubmed: 29437767
Nature. 1998 Jun 4;393(6684):478-80
pubmed: 9624004
Toxins (Basel). 2018 Nov 14;10(11):
pubmed: 30441807
Sci Rep. 2020 Nov 25;10(1):20560
pubmed: 33239692
J Immunol. 2005 May 15;174(10):6013-22
pubmed: 15879094
Clin Microbiol Rev. 2009 Apr;22(2):240-73, Table of Contents
pubmed: 19366914
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Nat Med. 1999 Jul;5(7):774-9
pubmed: 10395322
PLoS One. 2008;3(11):e3772
pubmed: 19020657
PLoS One. 2016 Mar 03;11(3):e0150606
pubmed: 26938654
Cancer Immun. 2007 Aug 13;7:12
pubmed: 17691714
Cancer Cell. 2016 Aug 8;30(2):324-336
pubmed: 27424807
J Immunol Methods. 2018 Aug;459:90-93
pubmed: 29859231
Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):541-551
pubmed: 31889004
Neuro Oncol. 2017 Aug 01;19(8):1047-1057
pubmed: 28371827
Neuron. 2019 Nov 6;104(3):442-449
pubmed: 31697921
Nat Immunol. 2020 Nov;21(11):1397-1407
pubmed: 32989328
Int Rev Cell Mol Biol. 2021;360:33-64
pubmed: 33962750
Nat Commun. 2019 Jan 25;10(1):448
pubmed: 30683885
Nat Commun. 2021 Jul 5;12(1):4127
pubmed: 34226552
Neuro Oncol. 2020 Oct 30;22(12 Suppl 2):iv1-iv96
pubmed: 33123732
Immunity. 2019 Jan 15;50(1):195-211.e10
pubmed: 30635237
Nature. 1998 Jun 4;393(6684):474-8
pubmed: 9624003
Nat Commun. 2020 Oct 27;11(1):5415
pubmed: 33110069
Nature. 2020 Aug;584(7822):624-629
pubmed: 32788723
Nat Med. 2019 Mar;25(3):477-486
pubmed: 30742122
Semin Immunol. 2009 Oct;21(5):257-64
pubmed: 19540774
Cancer Immunol Immunother. 2014 Aug;63(8):847-57
pubmed: 24878890
Neuro Oncol. 2015 Nov;17(11):1453-62
pubmed: 26008605
J Immunother Cancer. 2019 May 29;7(1):142
pubmed: 31142380
Science. 2014 Jun 20;344(6190):1396-401
pubmed: 24925914
Science. 2008 Nov 14;322(5904):1097-100
pubmed: 19008445
Neuro Oncol. 2021 Mar 25;23(3):356-375
pubmed: 33367885
J Exp Med. 2004 Jun 21;199(12):1659-69
pubmed: 15210744
Annu Rev Med. 2020 Jan 27;71:47-58
pubmed: 31412220
Cytometry A. 2015 Jul;87(7):636-45
pubmed: 25573116
Nat Med. 1999 Jul;5(7):780-7
pubmed: 10395323
Nat Rev Immunol. 2012 Feb 17;12(3):191-200
pubmed: 22343568
Immunity. 2020 May 19;52(5):825-841.e8
pubmed: 32396847
Neurooncol Pract. 2021 Nov 20;9(1):24-34
pubmed: 35096401
Biofactors. 2009 Nov-Dec;35(6):474-83
pubmed: 19904719
Oncol Lett. 2020 Nov;20(5):176
pubmed: 32934743
Sci Transl Med. 2021 May 19;13(594):
pubmed: 34011627
Cancer Immunol Res. 2015 May;3(5):557-66
pubmed: 25637366
Lab Invest. 2005 Mar;85(3):328-41
pubmed: 15716863
Science. 2002 Apr 12;296(5566):346-9
pubmed: 11923495
J Leukoc Biol. 2007 Jan;81(1):1-5
pubmed: 17032697
N Engl J Med. 2018 Jul 12;379(2):150-161
pubmed: 29943666
J Clin Neurosci. 2010 Jan;17(1):6-10
pubmed: 19926287
Nature. 1998 Jun 4;393(6684):480-3
pubmed: 9624005
Nat Med. 2018 Sep;24(9):1459-1468
pubmed: 30104766
Neuro Oncol. 2016 Aug;18(8):1120-8
pubmed: 26917236
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
J Immunol. 2020 Oct 1;205(7):1867-1877
pubmed: 32848036