MMP-cleavable linker platform for tumour-responsive homo- and heterobivalent antibody–drug conjugates
Herein we report the development of a novel linker platform for tumour-responsive antibody-drug conjugates. A series of functionalised homo- and heterobivalent BisFab conjugates have been synthesised, comprising an MMP-cleavable peptide sequence which facilitates selective monomerisation in the tumour microenvironment of the BisFab into two smaller cytotoxic species. The platform was then expanded to produce bispecific BisFab conjugates.
Authors
- Friederike M. Dannheim (ORCID: https://orcid.org/0000-0003-4651-0850)
- Thomas A. King (ORCID: https://orcid.org/0000-0001-6992-8016)
- Thomas Wharton (ORCID: https://orcid.org/0000-0002-9370-284X)
- Andrew J. Counsell (ORCID: https://orcid.org/0000-0003-0245-2329)
- Stephen J. Walsh (ORCID: https://orcid.org/0000-0002-3164-1519)
- Nicola Ashman (ORCID: https://orcid.org/0000-0003-4907-058X)
- David R. Spring (ORCID: https://orcid.org/0000-0001-7355-2824)
- Jason S. Carroll (ORCID: https://orcid.org/0000-0003-3643-0080)
- Mahri Park (ORCID: https://orcid.org/0000-0003-3973-6026)
Institutions
- University of Cambridge (GB)
- Cancer Research UK (GB)
- Cancer Research UK Cambridge Center (GB)
Publication Details
- Journal
- Chemical Science
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1039/d5sc06664f
- Citations
- 2
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 2.09
Funders
- AstraZeneca
- UK Research and Innovation
- Cancer Research UK
- Cystic Fibrosis Trust
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council
- Cancer Research UK Cambridge Institute, University of Cambridge