In vivo anti-MUC1
Animals
Antibodies, Monoclonal
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
Apoptosis
Cell Proliferation
Female
Humans
Immunotoxins
/ immunology
Mice
Mice, Nude
Mice, SCID
Mucin-1
/ chemistry
Pancreatic Neoplasms
/ drug therapy
Protein Domains
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Anti-MUC1 immunotherapy
Antibody–drug conjugation
MUC1 expression
Tumor antigens
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
22
07
2019
accepted:
08
03
2020
pubmed:
29
3
2020
medline:
1
7
2020
entrez:
29
3
2020
Statut:
ppublish
Résumé
Cleavage of the MUC1 glycoprotein yields two subunits, an extracellular alpha-subunit bound to a smaller transmembrane beta-subunit. Monoclonal antibodies (mAbs) directed against the MUC1 alpha-beta junction comprising the SEA domain, a stable cell-surface moiety, were generated. Sequencing of all seven anti-SEA domain mAbs showed that they clustered into four groups and sequences of all groups are presented here. mAb DMB5F3 with picomolar affinity for the MUC1 SEA target was selected for further evaluation. Immunohistochemical staining of a series of malignancies with DMB5F3 including lung, prostate, breast, colon, and pancreatic carcinomas revealed qualitative and qualitative differences between MUC1 expression on normal versus malignant cells: DMB5F3 strongly stained malignant cells in a near-circumferential pattern, whereas MUC1 in normal pancreatic and breast tissue showed only weak apical positivity of ductal/acinar cells. Humanized chimeric DMB5F3 linked to ZZ-PE38 (ZZ IgG-binding protein fused to Pseudomonas exotoxin) induced vigorous cytotoxicity of MUC1
Identifiants
pubmed: 32219500
doi: 10.1007/s00262-020-02547-2
pii: 10.1007/s00262-020-02547-2
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
Immunotoxins
0
MUC1 protein, human
0
Mucin-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1337-1352Subventions
Organisme : Israel Cancer Association
ID : 20112024
Organisme : Israel Science Foundation
ID : 1167/10
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