Prostate-Specific Membrane Antigen (PSMA) Targeted Bioorthogonal Therapy for Metastatic Prostate Cancer
Abstract
During the final year of the project we have tested and validated pretargeting delivery of mertansine drug carriers to prostate cancer using 5D3 monoclonal antibody and compared it with Fab2 fragments. In vitro studies in cultured prostate cancer cells has been completedand a paper was published in Molecular Pharmaceutics. Quantitative analysis of cell images allowed measurement of internalization rates of different pretargeting agent and drug carriers. Kinetics of internalization plays important role in the pretargeting concept, as the pretargeting component should be available on surface of targeted cells at the time of administration of the drug carrier component. For in vivo applications new pretargeting click-reactive components are needed and we have identified a 5D3 antibody fragment that retain extremely high PSMA binding affinity and has relatively long life-time on the cell surface before internalization, comparable with its in vivo pharmacokinetics. PET/MR imaging of PSMA pretargeting in prostate cancer models have been performed and suggested excellent physiological profile of the new system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2021
- Accession Number
- AD1118632
Entities
People
- Dmitri Artemov
Organizations
- Johns Hopkins University