Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment.
Antibodies, Monoclonal
/ adverse effects
Antineoplastic Agents, Immunological
/ adverse effects
Cytokines
/ blood
Feasibility Studies
Gangliosides
/ antagonists & inhibitors
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Inflammation Mediators
/ blood
Monitoring, Immunologic
Neoplasm Recurrence, Local
Neoplasm Staging
Neuroblastoma
/ blood
Predictive Value of Tests
Prospective Studies
Time Factors
Transplantation, Haploidentical
Treatment Outcome
GD2 antibody therapy
antibody-dependent cellular cytotoxicity
complement-dependent cytotoxicity
haploidentical allogeneic stem cell transplantation
immunomonitoring immunotherapy
neuroblastoma
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
02
04
2021
accepted:
16
06
2021
entrez:
9
8
2021
pubmed:
10
8
2021
medline:
28
10
2021
Statut:
epublish
Résumé
Haploidentical stem cell transplantation (haplo SCT) in Stage IV neuroblastoma relapsed patients has been proven efficacious, while immunotherapy utilizing the anti-GD2 antibody dinutuximab beta has become a standard treatment for neuroblastoma. The combinatorial therapy of haplo SCT and dinutuximab may potentiate the efficacy of the immunotherapy. To gain further understanding of the synergistic effects, functional immunomonitoring was assessed during the clinical trial CH14.18 1021 Antibody and IL2 After haplo SCT in Children with Relapsed Neuroblastoma (NCT02258815). Rapid immune reconstitution of the lymphoid compartment was confirmed, with clinically relevant dinutuximab serum levels found in all patients over the course of treatment. Only one patient developed human anti-chimeric antibodies (HACAs). In-patient monitoring revealed highly functional NK cell posttransplant capable of antibody-dependent cellular cytotoxicity (ADCC). Degranulation of NK cell subsets revealed a significant response increased by dinutuximab. This was irrespective of the KIR receptor-ligand constellation within the NK subsets, defined by the major KIR receptors CD158a, CD158b, and CD158e. Moreover, complement-dependent cytotoxicity (CDC) was shown to be an extremely potent effector-cell independent mechanism of tumor cell lysis, with a clear positive correlation to GD2 expression on the cancer cells as well as to the dinutuximab concentrations. The
Identifiants
pubmed: 34367149
doi: 10.3389/fimmu.2021.690467
pmc: PMC8339919
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
Cytokines
0
Gangliosides
0
Inflammation Mediators
0
ganglioside, GD2
65988-71-8
dinutuximab
7SQY4ZUD30
Banques de données
ClinicalTrials.gov
['NCT02258815']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
690467Informations de copyright
Copyright © 2021 Seitz, Flaadt, Mezger, Lang, Michaelis, Katz, Syring, Joechner, Rabsteyn, Siebert, Troschke-Meurer, Zumpe, Lode, Yang, Atar, Mast, Scheuermann, Heubach, Handgretinger, Lang and Schlegel.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Clin Cancer Res. 2018 Jan 1;24(1):189-196
pubmed: 28972044
MAbs. 2016;8(3):604-16
pubmed: 26785755
MAbs. 2018 Jan;10(1):55-61
pubmed: 29120699
Cancers (Basel). 2020 Jan 28;12(2):
pubmed: 32013055
Lancet Oncol. 2014 Jan;15(1):35-47
pubmed: 24314616
N Engl J Med. 2010 Sep 30;363(14):1324-34
pubmed: 20879881
J Immunol Methods. 2014 May;407:108-15
pubmed: 24727144
Oncoimmunology. 2016 Sep 26;5(11):e1235108
pubmed: 27999754
Onco Targets Ther. 2020 May 08;13:3903-3920
pubmed: 32440155
Lancet Oncol. 2018 Dec;19(12):1617-1629
pubmed: 30442501
Br J Haematol. 2014 Jun;165(5):688-98
pubmed: 24588540
Cancer Immunol Immunother. 2013 Jun;62(6):999-1010
pubmed: 23591980
PLoS One. 2015 Mar 20;10(3):e0120925
pubmed: 25793878
Blood. 2010 Oct 7;116(14):2411-9
pubmed: 20581313
J Clin Oncol. 2015 Sep 20;33(27):3008-17
pubmed: 26304901
Best Pract Res Clin Haematol. 2011 Sep;24(3):403-11
pubmed: 21925093
Front Pediatr. 2020 Dec 16;8:582820
pubmed: 33392114
Bone Marrow Transplant. 2019 Aug;54(Suppl 2):689-693
pubmed: 31431707
Cancers (Basel). 2018 Oct 17;10(10):
pubmed: 30336605
Lancet Oncol. 2017 Jul;18(7):946-957
pubmed: 28549783
Pediatr Blood Cancer. 2014 Jun;61(6):977-81
pubmed: 23970413
Cancer Res. 2004 Jul 1;64(13):4664-9
pubmed: 15231679
Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012
pubmed: 29307718
Science. 2002 Mar 15;295(5562):2097-100
pubmed: 11896281
Bone Marrow Transplant. 2019 Aug;54(Suppl 2):727-732
pubmed: 31431711
J Clin Oncol. 2009 Mar 1;27(7):1007-13
pubmed: 19171716
Nat Rev Dis Primers. 2016 Nov 10;2:16078
pubmed: 27830764
Blood. 2010 Apr 29;115(17):3437-46
pubmed: 20040760
Lancet Oncol. 2017 Apr;18(4):500-514
pubmed: 28259608
Blood. 2008 Nov 1;112(9):3574-81
pubmed: 18606875
Eur J Cancer. 1995;31A(2):261-7
pubmed: 7718335
Br J Haematol. 2006 Nov;135(4):524-32
pubmed: 17010105
J Clin Oncol. 1987 Sep;5(9):1430-40
pubmed: 3625258
PLoS One. 2014 Sep 16;9(9):e107692
pubmed: 25226154
Bone Marrow Transplant. 2019 Jan;54(1):53-62
pubmed: 29795418
J Clin Oncol. 2005 May 20;23(15):3447-54
pubmed: 15753458