Abstract 4442: Targeting ITGB4 with a topoisomerase I ADC: Preclinical antitumor activity in colorectal and head and neck cancers

Key Points

• This research aims to evaluate the antitumor activity and safety of GENA-120, an ITGB4-targeting antibody-drug conjugate.
• Utilized the GNOCLE™ platform to identify ITGB4 as a tumor-specific antigen.
• Developed GENA-120, consisting of a humanized anti-ITGB4 antibody, a hydrophilic linker, and a topoisomerase I inhibitor.
• Conducted in vitro assays to assess binding, internalization, and cytotoxic effects in cancer cell lines.
• Performed in vivo studies using xenograft models of colorectal and head & neck cancers.
• GENA-120 demonstrated high binding affinity and specific internalization into ITGB4-expressing cancer cells.
• The ADC showed potent cytotoxic activity and bystander effects in mixed cancer cell cultures.
• In vivo, GENA-120 exhibited significant antitumor activity in specific cancer xenograft models with no observed toxicities at high doses.