Targeted Delivery of TNF Potentiates the Antibody-Dependent Cell-Mediated Cytotoxicity of an Anti-Melanoma Immunoglobulin.
Animals
Antibodies, Monoclonal, Murine-Derived
/ administration & dosage
Antigens, Neoplasm
/ immunology
CHO Cells
Cell Line, Tumor
/ transplantation
Cricetulus
Drug Administration Schedule
Drug Screening Assays, Antitumor
Female
Humans
Immunoconjugates
/ administration & dosage
Immunoglobulin G
/ immunology
Melanoma, Experimental
/ drug therapy
Membrane Glycoproteins
/ immunology
Mice
Oxidoreductases
/ immunology
Recombinant Fusion Proteins
/ administration & dosage
Skin Neoplasms
/ drug therapy
Tumor Necrosis Factor-alpha
/ administration & dosage
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
25
07
2018
revised:
01
11
2018
accepted:
13
11
2018
pubmed:
14
12
2018
medline:
10
5
2020
entrez:
14
12
2018
Statut:
ppublish
Résumé
The recombinant murine IgG2a antibody TA99, directed against a melanoma antigen, was used to study combination modalities that potentiate antibody-dependent cell cytotoxicity. As previously reported, IgG2a(TA99) was extremely efficacious in preventing the growth of B16 lung metastases. However, the same antibody mediated only minimal tumor growth retardation when used to treat established neoplastic masses. The therapeutic activity of IgG2a(TA99) could be substantially enhanced by co-administration with an antibody-cytokine fusion (TA99-murine tumor necrosis factor [mTNF]), consisting of the TA99 antibody in single-chain variable fragment format fused to murine TNF. This fusion protein efficiently killed endothelial cells in vitro and displayed only minimal activity against B16 melanoma cells. In vivo, TA99-mTNF boosted the influx of natural killer cells and macrophages into B16 melanoma lesions. Therapy studies with two different administration schedules showed that the combination of TA99-mTNF and IgG2a(TA99) was superior to the individual products used as single agents. The combination treatment converted most of the tumor mass into a necrotic lesion, but a vital tumor rim eventually regrew, even when dacarbazine was included in the therapeutic regimen. The treatment modality described in this article may be applicable to the treatment of melanoma patients, given the specificity of the gp75 antigen and its conservation across species.
Identifiants
pubmed: 30543899
pii: S0022-202X(18)32928-2
doi: 10.1016/j.jid.2018.11.028
pmc: PMC6986903
mid: EMS85516
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Murine-Derived
0
Antigens, Neoplasm
0
Immunoconjugates
0
Immunoglobulin G
0
Membrane Glycoproteins
0
Recombinant Fusion Proteins
0
Tnf protein, mouse
0
Tumor Necrosis Factor-alpha
0
Oxidoreductases
EC 1.-
TYRP1 protein, human
EC 1.14.18.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1339-1348Subventions
Organisme : Swiss National Science Foundation
ID : 163479
Pays : Switzerland
Organisme : European Research Council
ID : 670603
Pays : International
Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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