Hydrophilic Monomethyl Auristatin E Derivatives as Novel Candidates for the Design of Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are promising state-of-the-art biopharmaceutical drugs for selective drug-delivery applications and the treatment of diseases such as cancer. The idea behind the ADC technology is remarkable as it combines the highly selective targeting capacity of monoclonal antibodi...

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Bibliographic Details
Published in:Separations 2018-12, Vol.6 (1), p.1
Main Authors: Ekholm, Filip, Ruokonen, Suvi-Katriina, Redón, Marina, Pitkänen, Virve, Vilkman, Anja, Saarinen, Juhani, Helin, Jari, Satomaa, Tero, Wiedmer, Susanne
Format: Article
Language:English
Subjects:
Antibodies
antibody-drug conjugate
Biocompatibility
biopharmaceutical
Breast cancer
Cancer
Capillary electrophoresis
Carbohydrates
Chromatography
Conjugates
Contact angle
Cytotoxicity
Electrokinetics
Hydrophilicity
Hydrophobicity
Leukemia
Lymphoma
micellar electrokinetic chromatography
Monoclonal antibodies
Polyethylene glycol
Retention
Sodium
Surfactants
Warheads
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Summary:Antibody-drug conjugates (ADCs) are promising state-of-the-art biopharmaceutical drugs for selective drug-delivery applications and the treatment of diseases such as cancer. The idea behind the ADC technology is remarkable as it combines the highly selective targeting capacity of monoclonal antibodies with the cancer-killing ability of potent cytotoxic agents. The continuous development of improved ADCs requires systematic studies on the nature and effects of warhead modification. Recently, we focused on the hydrophilic modification of monomethyl auristatin E (MMAE), the most widely used cytotoxic agent in current clinical trial ADCs. Herein, we report on the use of micellar electrokinetic chromatography (MEKC) for studying the hydrophobic character of modified MMAE derivatives. Our data reveal a connection between the hydrophobicity of the modified warheads as free molecules and their cytotoxic activity. In addition, MMAE-trastuzumab ADCs were constructed and evaluated in preliminary cytotoxic assays.
ISSN:2297-8739
2297-8739
DOI:10.3390/separations6010001