An Efficient Conjugation Approach for Coupling Drugs to Native Antibodies via the PtII Linker Lx for Improved Manufacturability of Antibody–Drug Conjugates

The PtII linker [ethylenediamineplatinum(II)]2+, coined Lx, has emerged as a novel non‐conventional approach to antibody–drug conjugates (ADCs) and has shown its potential in preclinical in vitro and in vivo benchmark studies. A crucial improvement of the Lx conjugation reaction from initially...

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Published in:Angewandte Chemie 2021-02, Vol.133 (6), p.3045-3052
Main Authors: Merkul, Eugen, Muns, Joey A., Sijbrandi, Niels J., Houthoff, Hendrik‐Jan, Nijmeijer, Bart, Rheenen, Gerro, Reedijk, Jan, Dongen, Guus A. M. S.
Format: Article
Language:English
Subjects:
Antibodies
antibody–drug conjugates
Chemistry
Conjugates
Conjugation
Efficiency
In vivo methods and tests
Inorganic salts
Iodides
linkers
Manufacturability
platinum
Selectivity
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container_issue 6
container_start_page 3045
container_title Angewandte Chemie
container_volume 133
creator Merkul, Eugen
Muns, Joey A.
Sijbrandi, Niels J.
Houthoff, Hendrik‐Jan
Nijmeijer, Bart
Rheenen, Gerro
Reedijk, Jan
Dongen, Guus A. M. S.
description The PtII linker [ethylenediamineplatinum(II)]2+, coined Lx, has emerged as a novel non‐conventional approach to antibody–drug conjugates (ADCs) and has shown its potential in preclinical in vitro and in vivo benchmark studies. A crucial improvement of the Lx conjugation reaction from initially
doi_str_mv 10.1002/ange.202011593
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Using this iodide effect, we developed a general and highly practical conjugation procedure that is scalable: our lead Lx‐ADC was produced on a 5 g scale with an outstanding conjugation efficiency of 89 %. PtII complexes containing a payload, a bidentate ligand, and a halido leaving ligand (Cl−, Br− or I−) can be conjugated to native monoclonal antibodies in a very efficient way by using iodide salts, such as NaI, as simple inorganic additives to the aqueous conjugation mixtures. 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subjects Antibodies
antibody–drug conjugates
Chemistry
Conjugates
Conjugation
Efficiency
In vivo methods and tests
Inorganic salts
Iodides
linkers
Manufacturability
platinum
Selectivity
title An Efficient Conjugation Approach for Coupling Drugs to Native Antibodies via the PtII Linker Lx for Improved Manufacturability of Antibody–Drug Conjugates
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