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Methods for site-specific drug conjugation to antibodies
Open accessAbstract
Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however,the importance of conjugate homogeneity has been realized. The current methods for drug attachment lead to a heterogeneous mixture, and some populations of that mixture have poor in vivo performance. New methods for site-specific drug attachment lead to more homogeneous conjugates and allow control of the site of drug attachment. These subtle improvements can have profound effects on in vivo efficacy and therapeutic index. This review examines current methods for site-specific drug conjugation to antibodies, and compares in vivo results with their non-specifically conjugated counterparts. The apparent improvement in pharmacokinetics and the reduced off target toxicity warrant further development of this site-specific modification approach for future ADC development.
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Cites
Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality
Sletten, E. M., & Bertozzi, C. R. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200900942 · Cited by 3,165
Drug penetration in solid tumours
Minchinton, A. I., & Tannock, I. F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1893 · Cited by 2,805
Cited by
Antibody–drug conjugates for cancer
Chau, C. H., Steeg, P. S., & Figg, W. D. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31774-x · Cited by 816
Agarwal, P., & Bertozzi, C. R. (2015) · Bioconjugate Chemistry · doi:10.1021/bc5004982 · Cited by 605
Mechanisms of ADC Toxicity and Strategies to Increase ADC Tolerability
Nguyen, T. D., Bordeau, B. M., & Balthasar, J. P. (2023) · Cancers · doi:10.3390/cancers15030713 · Cited by 441
Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant
Williams, R. M., Lee, C., Galassi, T. V., Harvey, J. D., Leicher, R., Sirenko, M., Dorso, M. A., Shah, J., Olvera, N., Dao, F., et al. (2018) · Science Advances · doi:10.1126/sciadv.aaq1090 · Cited by 183
Metadata
- Authors
- Behrens, C. R., & Liu, B.
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2013-09-27
- Volume
- 6
- Issue
- 1
- Pages
- 46-53
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- OpenAlex
- W1983386052
- Cited by
- 171
- References
- 2
- FWCI
- 14.97
- Type
- journal article
- Language
- en
- Open access
- gold
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
