Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy
Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy
We improve the potency of antibody–drug conjugates (ADCs) containing the human epidermal growth factor receptor 2 (HER2)-specific antibody pertuzumab by substantially reducing their affinity for HER2 at acidic endosomal pH relative to near neutral pH. These engineered pertuzumab variants show increased lysosomal delivery and cytotoxicity towards tumor cells expressing intermediate HER2 levels. In HER2int xenograft tumor models in mice, the variants show higher therapeutic efficacy than the parent ADC and a clinically approved HER2-specific ADC.
523-526
Kang, Jeffrey C.
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Sun, Wei
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Khare, Priyanka
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Karimi, Mostafa
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Wang, Xiaoli
b4716dc4-ee38-4e74-8690-1f027ccf080b
Shen, Yang
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Ober, R.J.
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Ward, E. Sally
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1 April 2019
Kang, Jeffrey C.
a3dfd242-a85c-475e-9b98-a6a79db7a93c
Sun, Wei
000b1f51-3244-44c5-b309-54d3b01c9089
Khare, Priyanka
81db6b4f-ee24-4dcf-84e3-42b53f367cde
Karimi, Mostafa
2ecfafb4-a325-4392-b5d8-d4ff85f2c617
Wang, Xiaoli
b4716dc4-ee38-4e74-8690-1f027ccf080b
Shen, Yang
b62d5af5-48bc-41d1-88be-c364f6129a9f
Ober, R.J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Kang, Jeffrey C., Sun, Wei, Khare, Priyanka, Karimi, Mostafa, Wang, Xiaoli, Shen, Yang, Ober, R.J. and Ward, E. Sally
(2019)
Engineering a HER2-specific antibody–drug conjugate to increase lysosomal delivery and therapeutic efficacy.
Nature Biotechnology, 37 (5), .
(doi:10.1038/s41587-019-0073-7).
Abstract
We improve the potency of antibody–drug conjugates (ADCs) containing the human epidermal growth factor receptor 2 (HER2)-specific antibody pertuzumab by substantially reducing their affinity for HER2 at acidic endosomal pH relative to near neutral pH. These engineered pertuzumab variants show increased lysosomal delivery and cytotoxicity towards tumor cells expressing intermediate HER2 levels. In HER2int xenograft tumor models in mice, the variants show higher therapeutic efficacy than the parent ADC and a clinically approved HER2-specific ADC.
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Accepted/In Press date: 20 February 2019
e-pub ahead of print date: 1 April 2019
Published date: 1 April 2019
Identifiers
Local EPrints ID: 430711
URI: http://eprints.soton.ac.uk/id/eprint/430711
ISSN: 1087-0156
PURE UUID: e493e07e-3fd4-4de2-ae70-363a5a64d965
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Date deposited: 08 May 2019 16:30
Last modified: 16 Mar 2024 07:38
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Contributors
Author:
Jeffrey C. Kang
Author:
Wei Sun
Author:
Priyanka Khare
Author:
Mostafa Karimi
Author:
Xiaoli Wang
Author:
Yang Shen
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