Enhanced Targeting of Acute Myeloid Leukemia with CD7 and CD33 Dual-Targeting Antibody Drug Conjugates

A study has identified that in 25% of acute myeloid leukemia (AML) cases, CD33 and CD7 markers are co-expressed, suggesting a potential for a bispecific antibody drug conjugate (ADC) to target these cells more selectively than the existing anti-CD33 ADC, gemtuzumab ozogamicin. Researchers produced anti-CD7 and anti-CD33 Fabs in HEK293 cells and assessed their binding strengths. They created a Bi-Fab using click chemistry and linked it to two different cytotoxic agents. The cytotoxicity of the resulting Bi-Fab drug conjugates was tested on specific cell lines and compared to monospecific conjugates and gemtuzumab drug conjugates for selectivity.

The lead Bi-Fab, BVX130-mcMMAF, demonstrated no cytotoxicity to resting T-cells and did not affect colony formation in myeloid progenitor cells. In a xenograft model using SCID mice, BVX130-mcMMAF showed significant tumor growth inhibition with no observed adverse effects. The findings indicate that the Bi-Fab drug conjugates are highly effective against CD7+CD33+ cells both in vitro and in vivo, with greater selectivity than their monospecific counterparts. This supports the advancement of bispecific ADCs targeting CD7 and CD33 for AML treatment.

The research was presented by Richard Bethell and colleagues at the American Association for Cancer Research Annual Meeting in 2020.