Secreted Gal-3BP is a novel promising target for non-internalizing Antibody-Drug Conjugates.
Galectin-3-binding protein
Maytansinoid derivatives
Melanoma
Non-internalizing ADC
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
28 01 2019
28 01 2019
Historique:
received:
16
10
2018
revised:
11
12
2018
accepted:
12
12
2018
pubmed:
17
12
2018
medline:
21
3
2020
entrez:
17
12
2018
Statut:
ppublish
Résumé
Galectin-3-binding protein (Gal-3BP) has been identified as a cancer and metastasis-associated, secreted protein that is expressed by the large majority of cancers. The present study describes a special type of non-internalizing antibody-drug-conjugates that specifically target Gal-3BP. Here, we show that the humanized 1959 antibody, which specifically recognizes secreted Gal-3BP, selectively localized around tumor but not normal cells. A site specific disulfide linkage with thiol-maytansinoids to unpaired cysteine residues of 1959, resulting in a drug-antibody ratio of 2, yielded an ADC product, which cured A375m melanoma bearing mice. ADC products based on the non-internalizing 1959 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed and secreted by several cancers, while being present at low levels in most normal adult tissues.
Identifiants
pubmed: 30553852
pii: S0168-3659(18)30721-1
doi: 10.1016/j.jconrel.2018.12.018
pii:
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
Immunoconjugates
0
LGALS3BP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
176-184Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.