Anti-TROP2 antibody-drug conjugates comprising PNU-159682 derivatives
Patent Information
- Application Number
- MDE20260214T
- Authority / Receiving Office
- MD · MD
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-04-19
- Publication Date
- 2026-03-31
AI Technical Summary
Current anti-TROP2 antibody-drug conjugates face challenges with toxicity and limited cancer specificity due to binding to both high and low TROP2-expressing cells, leading to unwanted adverse effects and requiring frequent dosing, which affects their efficacy in treating TROP2-associated cancers.
Development of avidity-tuned and rehumanized anti-TROP2 antibodies with reduced hydrophobicity, specifically binding to high TROP2-expressing cells by conjugating them with derivatives of the anthracycline metabolite PNU-159682, creating antibody-drug conjugates that preferentially target TROP2high cells while minimizing binding to TROP2low cells.
The resulting antibody-drug conjugates demonstrate enhanced cancer specificity and reduced toxicity, maintaining antitumor activity comparable to existing antibodies while minimizing off-target effects, thus improving the therapeutic index for TROP2-associated cancers.