Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates

By Ben-Quan Shen, Keyang Xu, Luna Liu, H. Raab, S. Bhakta, Margaret Kenrick, K. Parsons-Reponte, Janet Y. Tien, Shang‐Fan Yu, Elaine Mai and 23 more. Nature Biotechnology, 2012

928 citations recorded by the source corpus.

Subfields: Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/05543780393df675ae4ce4d6f5b170df3e3e553e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. Paul Polakis

In Radiology, Nuclear Medicine and Imaging

1. M. Finn
2. Paul Polakis
3. S. Bhakta
4. Craig S Mckay
5. S. Panowski
6. Jagath R Junutula
7. H. Raab

Citations in the corpus

• Site-specific antibody drug conjugates for cancer therapy (2013, methodology): “Recently, the site-specific approach has also allowed in-depth study of how the conjugation site modulates in vivo ADC stability and therapeutic activity.(50) In this study, engineered cysteine technology was used to generate three different trastuzumab THIOMABs, one with a highly accessible conjuga”
• Antibody Drug Conjugates for Cancer Therapy (2016, background): “A comparison of THIOMABs containing MMAE appended to distinct sites, revealed a pronounced impact of conjugation site on linker-drug stability, which in turn, dramatically impacted efficacy (Shen et al., 2012).”
• Antibody drug conjugate: the “biological missile” for targeted cancer therapy (2022, background): “The stability of such coupling is sometimes insufficient and this causes premature payload release and thus off-target toxicity.(97,98) Furthermore, it is difficult to guarantee payload connection to consistent sites on the antibody and it is also difficult to achieve a homogeneous DAR that are favo”
• Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation (2014, background): “, 2009a; Stenzel, 2012) are subject to competing reactions with other nucleophilic amino acids (usually lysine and histidine) to an extent that can be highly variable and occasionally substantial (Baldwin and Kiick, 2011; Heukeshoven, 1980; Lewis and Shively, 1998)(Alley et al., 2008; Shen et al., 2”