Journal
PHARMACEUTICAL RESEARCH
Volume 32, Issue 11, Pages 3494-3507Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-015-1624-3
Keywords
5T4; A1-mcMMAF; ADC; antibody-drug conjugate; site-specific conjugation
Ask authors/readers for more resources
Antibody-drug conjugates (ADCs) represent a promising modality for the treatment of cancer. The therapeutic strategy is to deliver a potent drug preferentially to the tumor and not normal tissues by attaching the drug to an antibody that recognizes a tumor antigen. The selection of antigen targets is critical to enabling a therapeutic window for the ADC and has proven to be surprisingly complex. We surveyed the tumor and normal tissue expression profiles of the targets of ADCs currently in clinical development. Our analysis demonstrates a surprisingly broad range of expression profiles and the inability to formalize any optimal parameters for an ADC target. In this context, we discuss additional considerations for ADC target selection, including interdependencies among biophysical properties of the drug, biological functions of the target and strategies for clinical development. The TPBG (5T4) oncofetal antigen and the anti-TPBG ADC A1-mcMMAF are highlighted to demonstrate the relevance of the target's biological function. Emerging platform technologies and novel biological insights are expanding ADC target space and transforming strategies for target selection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available