Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index

By Jagath R Junutula, H. Raab, Suzanna Clark, S. Bhakta, D. Leipold, Sylvia Weir, Yvonne Chen, M. Simpson, S. Tsai, M. Dennis and 21 more. Nature Biotechnology, 2008

1,242 citations recorded by the source corpus.

Subfields: Oncology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/9d42223ce28f1185dddb3f4f78d5cb7e47c31078

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. M. Sliwkowski
2. Charles Dumontet
3. Paul Polakis
4. M. Lacouture

In Radiology, Nuclear Medicine and Imaging

1. M. Sliwkowski
2. Z. An
3. Paul Polakis
4. S. Bhakta
5. K. Tsuchikama
6. P. Senter
7. Jagath R Junutula
8. H. Raab

Citations in the corpus

• Strategies and challenges for the next generation of therapeutic antibodies (2010, background): “IgGs have also been engineered to contain unique drug conjugation positions to obtain uniform and more homogeneous drug conjugates (such as thiomab–drug conjugates, which have a uniform stoichiometry of approximately two coupled drugs per antibody molecul”
• Antibody Drug Conjugates for Cancer Therapy (2016, background): “The prototypical version involved substitution of a specified amino acid in the IgG1 heavy or light chain with a cysteine, resulting in two exclusive sites of conjugation per antibody tetramer (Junutula et al., 2008).”
• Antibody–drug conjugates come of age in oncology (2023, background): “(4) release of payload within the cytoplasm; and (5) interaction with target.”
• Antibody-drug conjugates: recent advances in conjugation and linker chemistries (2016, background): “Junutula and co-workers introduced two new cysteine residues (one per heavy chain) for selective antibody attachment (Junutula et al., 2008).”
• Antibody drug conjugate: the “biological missile” for targeted cancer therapy (2022, methodology): “Hence, an appropriate selection of target antigen is the first consideration for the designation of ADC.”
• Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates (2012, methodology): “Thiol-maleimide chemistry is a commonly used method, whereby a cysteine residue, either native or engineered, is used for conjugatio”