Stoichiometric antibody-polymer-drug conjugate for effective low-dose treatment of breast cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F25%3A00641227" target="_blank" >RIV/61389013:_____/25:00641227 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.biomac.5c00598" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.biomac.5c00598</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.biomac.5c00598" target="_blank" >10.1021/acs.biomac.5c00598</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Stoichiometric antibody-polymer-drug conjugate for effective low-dose treatment of breast cancer

Popis výsledku v původním jazyce

In the past two decades, antibody–drug conjugates (ADCs) have emerged as highly effective targeted therapeutics against cancers. One current path to improve ADCs is to increase the amount of cytotoxic payload delivered to cancer cells by conjugating antibodies with a soluble polymer bearing several drug molecules. However, this approach is challenging due to the high molecular weight of the polymer and the need to strictly control the degree of conjugation to maintain favorable pharmacokinetic and binding profiles. Here, we build from the recent development brought to our automated stoichiometric conjugation device to tackle this challenge. We produced a new format of ADC-like targeted therapy: monoconjugated Antibody–Polymer–Drug Conjugates (APDCs) with enzyme-cleavable linkers, designed to achieve selective delivery of the cytotoxic MMAE to HER2+ cancer cells. We showed the selectivity of our conjugates for HER2+ over HER2– cells in vitro and demonstrated their efficiency in vivo in a SKBR-3-xenografted mouse (NOD-SCID) model.

Název v anglickém jazyce

Stoichiometric antibody-polymer-drug conjugate for effective low-dose treatment of breast cancer

Popis výsledku anglicky

In the past two decades, antibody–drug conjugates (ADCs) have emerged as highly effective targeted therapeutics against cancers. One current path to improve ADCs is to increase the amount of cytotoxic payload delivered to cancer cells by conjugating antibodies with a soluble polymer bearing several drug molecules. However, this approach is challenging due to the high molecular weight of the polymer and the need to strictly control the degree of conjugation to maintain favorable pharmacokinetic and binding profiles. Here, we build from the recent development brought to our automated stoichiometric conjugation device to tackle this challenge. We produced a new format of ADC-like targeted therapy: monoconjugated Antibody–Polymer–Drug Conjugates (APDCs) with enzyme-cleavable linkers, designed to achieve selective delivery of the cytotoxic MMAE to HER2+ cancer cells. We showed the selectivity of our conjugates for HER2+ over HER2– cells in vitro and demonstrated their efficiency in vivo in a SKBR-3-xenografted mouse (NOD-SCID) model.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biomacromolecules

ISSN

1525-7797

e-ISSN

1526-4602

Svazek periodika

26

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

7309-7318

Kód UT WoS článku

001592239700001

EID výsledku v databázi Scopus

2-s2.0-105021118665