Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 04 2023
25 04 2023
Historique:
received:
03
02
2022
accepted:
31
03
2023
medline:
17
5
2023
pubmed:
15
5
2023
entrez:
15
5
2023
Statut:
epublish
Résumé
Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.
Identifiants
pubmed: 37185332
doi: 10.1038/s41467-023-37811-3
pii: 10.1038/s41467-023-37811-3
pmc: PMC10130092
doi:
Substances chimiques
chondroitin sulfate proteoglycan 4
0
Proteoglycans
0
Antigens
0
Chondroitin Sulfate Proteoglycans
0
Antibodies, Monoclonal
0
Immunoglobulin E
37341-29-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2192Subventions
Organisme : Cancer Research UK
ID : C30122/A15774
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
J Immunol. 2016 Oct 1;197(7):2583-8
pubmed: 27566822
Cancer Immunol Immunother. 2012 Dec;61(12):2295-309
pubmed: 22692757
J Allergy Clin Immunol Pract. 2018 Sep - Oct;6(5):1628-1636.e2
pubmed: 29339127
Cancer Res. 1987 May 1;47(9):2474-80
pubmed: 3552215
Nature. 1985 Mar 21-27;314(6008):268-70
pubmed: 2580239
Eur J Immunol. 1999 Nov;29(11):3527-37
pubmed: 10556807
Eur J Nucl Med. 1998 Nov;25(11):1489-94
pubmed: 9799344
J Immunother Cancer. 2014 Aug 19;2:25
pubmed: 25197555
J Immunol Methods. 2007 Jun 30;323(2):160-71
pubmed: 17531261
J Clin Invest. 1990 Dec;86(6):2136-44
pubmed: 2254463
Cancer Res. 2010 Apr 15;70(8):3027-33
pubmed: 20395199
J Allergy Clin Immunol Pract. 2016 Mar-Apr;4(2):338-40
pubmed: 26725157
Cancer Res. 2017 Jun 1;77(11):2779-2783
pubmed: 28526770
EBioMedicine. 2019 May;43:67-81
pubmed: 30956175
Cancer Res. 2007 Apr 1;67(7):3406-11
pubmed: 17409451
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
J Allergy Clin Immunol. 2018 Apr;141(4):1519-1523.e9
pubmed: 29360527
Pigment Cell Melanoma Res. 2011 Dec;24(6):1148-57
pubmed: 22004131
Cancer Immunol Immunother. 1991;34(2):90-6
pubmed: 1760821
BMC Cancer. 2013 Apr 17;13:195
pubmed: 23594731
Cancer Res. 2017 Mar 1;77(5):1127-1141
pubmed: 28096174
Clin Exp Immunol. 2008 Sep;153(3):401-9
pubmed: 18803764
Cancer Res. 1992 May 1;52(9):2497-503
pubmed: 1373670
Front Bioeng Biotechnol. 2019 Sep 25;7:242
pubmed: 31632959
Antibodies (Basel). 2020 Oct 16;9(4):
pubmed: 33081206
Int J Mol Sci. 2018 Mar 21;19(4):
pubmed: 29561763
MAbs. 2020 Jan-Dec;12(1):1685349
pubmed: 31769737
Allergy. 2018 Dec;73(12):2328-2341
pubmed: 29654623
Cell. 2019 Feb 7;176(4):775-789.e18
pubmed: 30595452
Cytotherapy. 2009;11(5):527-33
pubmed: 19462316
Cancer Immunol Immunother. 2012 Jul;61(7):991-1003
pubmed: 22127364
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Cells. 2020 Jul 07;9(7):
pubmed: 32645919
Nat Biotechnol. 2020 Jun;38(6):675-678
pubmed: 32444850
J Clin Invest. 2013 Apr;123(4):1457-74
pubmed: 23454746
Clin Cancer Res. 2018 Mar 15;24(6):1260-1270
pubmed: 29127120
Cancers (Basel). 2020 Apr 22;12(4):
pubmed: 32331483
Front Immunol. 2018 Jan 10;8:1911
pubmed: 29375561
Cancers (Basel). 2020 Nov 15;12(11):
pubmed: 33203088
Oncoimmunology. 2021 Sep 6;10(1):1966970
pubmed: 34513315
J Natl Cancer Inst. 2010 Oct 6;102(19):1496-512
pubmed: 20852124
Allergy. 2019 Oct;74(10):1985-1989
pubmed: 30964550
Crit Rev Immunol. 2004;24(4):267-96
pubmed: 15588226
Science. 1994 Jun 24;264(5167):1876-7
pubmed: 8009216
J Allergy Clin Immunol. 2014 Sep;134(3):645-52
pubmed: 25065721
Cell Rep. 2015 Mar 10;10(9):1487-1495
pubmed: 25753415
Cancer Immunol Immunother. 2009 Jun;58(6):915-30
pubmed: 18941743
Clin Cancer Res. 2012 Oct 1;18(19):5352-63
pubmed: 22893632
J Invest Dermatol. 1996 Aug;107(2):164-70
pubmed: 8757757
Clin Cancer Res. 2014 Feb 15;20(4):962-71
pubmed: 24334762
J Nucl Med. 1989 Mar;30(3):390-7
pubmed: 2472474
Science. 2017 Aug 18;357(6352):
pubmed: 28818916
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Annu Rev Immunol. 1991;9:457-92
pubmed: 1910686
J Immunother Cancer. 2021 Jun;9(6):
pubmed: 34112739
Sci Transl Med. 2018 Feb 28;10(430):
pubmed: 29491184
J Immunol. 2007 Sep 1;179(5):2832-43
pubmed: 17709497
Nature. 1994 Jan 13;367(6459):183-6
pubmed: 8114916
Allergy. 2020 Aug;75(8):2069-2073
pubmed: 32086828
Int Arch Allergy Immunol. 2018;177(3):274-280
pubmed: 30041169
Eur J Immunol. 2003 Apr;33(4):1030-40
pubmed: 12672069
J Immunol. 1985 Jul;135(1):696-702
pubmed: 2582052
Hum Gene Ther. 2006 Nov;17(11):1134-43
pubmed: 17052145
Clin Cancer Res. 2020 Dec 1;26(23):6321-6334
pubmed: 32900797
Dermatology. 1995;191(2):119-23
pubmed: 8520057
Oncol Rep. 2021 Apr;45(4):
pubmed: 33649790
World Allergy Organ J. 2019 Jul 29;12(7):100044
pubmed: 31388397
J Allergy Clin Immunol. 2018 Sep;142(3):973-976.e11
pubmed: 29746883