ErbB2 Targeted Epigenetic Modulation: Anti-tumor Efficacy of the ADC Trastuzumab-HDACi ST8176AA1.
ADC (antibody drug conjugate)
ErbB2
HDACi (Histone deacetylase inhibitor)
solid tumors
trastuzumab
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2019
2019
Historique:
received:
24
09
2019
accepted:
19
12
2019
entrez:
11
2
2020
pubmed:
11
2
2020
medline:
11
2
2020
Statut:
epublish
Résumé
Targeted therapy using monoclonal antibodies conjugated to toxins is gaining space in the treatment of cancer. Here, we report the anti-tumor effect of a new antibody drug conjugate (ADC) delivering a HDAC inhibitor to ErbB2+ solid tumors. Trastuzumab was partially reduced with tris [2-carboxyethyl] phosphine (TCEP) and conjugated to ST7464AA1, the active form of the prodrug HDAC inhibitor ST7612AA1, through a maleimide-thiol linker to obtain the Antibody Drug Conjugate (ADC) ST8176AA1. The average drug/antibody ratio (DAR) was 4.5 as measured by hydrophobic interaction chromatography (HIC). Binding of ST8176AA1 to ErbB2 receptor and internalization in tumor cells were investigated by enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), cytofluorimetry, and High Content Screening (HCS) Imaging. The biological activity of the ADC was evaluated
Identifiants
pubmed: 32039017
doi: 10.3389/fonc.2019.01534
pmc: PMC6989603
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1534Informations de copyright
Copyright © 2020 Milazzo, Vesci, Anastasi, Chiapparino, Rosi, Giannini, Taddei, Cini, Faltoni, Petricci, Battistuzzi, Salvini, Carollo and De Santis.
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