Abstract 5635: Rational design of a bispecific ADC targeting ITGB4 and TROP2 for co-expressing solid tumors

Key Points

• The main goal is to create a bispecific antibody-drug conjugate (ADC) targeting ITGB4 and TROP2 for better treatment of co-expressing solid tumors.
• Identified ITGB4 as a tumor-specific antigen using the GNOCLE™ platform.
• Designed a bispecific ADC by combining sacituzumab and anti-ITGB4 antibody GENA-120B17.
• Developed 1+1 and 2+2 valency formats for optimized efficacy.
• Conjugated bispecific antibodies with a cleavable linker to cytotoxic agents.
• Evaluated in vitro cytotoxicity in double-positive cancer cell lines and normal cells.
• Bispecific ADCs showed enhanced internalization in ITGB4/TROP2 double-positive cells.
• Demonstrated superior in vitro cytotoxicity compared to monospecific ADCs.
• Maintained a safer profile in normal cells, indicating a broader therapeutic index.

Abstract