U3-1402, a Novel HER3-Targeting Antibody-Drug Conjugate, for the Treatment of Colorectal Cancer.
Animals
Antibodies, Monoclonal, Humanized
/ chemistry
Broadly Neutralizing Antibodies
/ chemistry
Camptothecin
/ analogs & derivatives
Cell Line, Tumor
Cell Proliferation
Cell Survival
/ drug effects
Colorectal Neoplasms
/ drug therapy
Female
Gene Expression Regulation, Neoplastic
/ drug effects
HCT116 Cells
Humans
Immunoconjugates
/ administration & dosage
Mice
Receptor, ErbB-3
/ antagonists & inhibitors
Up-Regulation
/ drug effects
Xenograft Model Antitumor Assays
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
28
04
2019
revised:
28
06
2019
accepted:
02
08
2019
pubmed:
10
8
2019
medline:
2
6
2020
entrez:
10
8
2019
Statut:
ppublish
Résumé
HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I inhibitor, DX-8951 derivative (DXd). The sensitivity of DXd was evaluated by a growth inhibition assay. The antitumor activity of U3-1402 was evaluated in a murine xenograft model in which its effects on cells, with a range of HER3 expression levels, were compared with those of patritumab alone, irinotecan, control-ADC, and saline. In the growth inhibition assay, all colorectal cancer cell lines were sensitive to DXd. In the tumor xenograft model, significant tumor regression with U3-1402 was observed both in the DiFi cell line (high HER3 expression;
Identifiants
pubmed: 31395690
pii: 1535-7163.MCT-19-0452
doi: 10.1158/1535-7163.MCT-19-0452
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Broadly Neutralizing Antibodies
0
Immunoconjugates
0
patritumab
86780VJI1Q
ERBB3 protein, human
EC 2.7.10.1
Receptor, ErbB-3
EC 2.7.10.1
exatecan
OC71PP0F89
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2043-2050Informations de copyright
©2019 American Association for Cancer Research.