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A homogeneous high-DAR antibody–drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides

Authors :
Neelie Zacharias
Vladimir N. Podust
Kimberly K. Kajihara
Douglas Leipold
Geoffrey Del Rosario
Desiree Thayer
Emily Dong
Maciej Paluch
David Fischer
Kai Zheng
Corinna Lei
Jintang He
Carl Ng
Dian Su
Luna Liu
Shabkhaiz Masih
William Sawyer
Jeff Tinianow
Jan Marik
Victor Yip
Guangmin Li
Josefa Chuh
J. Hiroshi Morisaki
Summer Park
Bing Zheng
Hilda Hernandez-Barry
Kelly M. Loyet
Min Xu
Katherine R. Kozak
Gail Lewis Phillips
Ben-Quan Shen
Cong Wu
Keyang Xu
Shang-Fan Yu
Amrita Kamath
Rebecca K. Rowntree
Dorothea Reilly
Thomas Pillow
Andrew Polson
Volker Schellenberger
Wouter L. W. Hazenbos
Jack Sadowsky
Source :
Chemical Science. 13:3147-3160
Publication Year :
2022
Publisher :
Royal Society of Chemistry (RSC), 2022.

Abstract

The antibody-drug conjugate (ADC) is a well-validated modality for the cell-specific delivery of small molecules with impact expanding rapidly beyond their originally-intended purpose of treating cancer. However, antibody-mediated delivery (AMD) remains inefficient, limiting its applicability to targeting highly potent payloads to cells with high antigen expression. Maximizing the number of payloads delivered per antibody is one key way in which delivery efficiency can be improved, although this has been challenging to carry out; with few exceptions, increasing the drug-to-antibody ratio (DAR) above ∼4 typically destroys the biophysical properties and

Subjects

Subjects :
General Chemistry

Details

ISSN :
20416539 and 20416520
Volume :
13
Database :
OpenAIRE
Journal :
Chemical Science
Accession number :
edsair.doi.dedup.....01bce602efd8f14a1021c22dad6d1512