Optimized B7-H3 ADC with PBD payload for solid tumors

A genetically and chemically engineered antibody-drug conjugate (ADC) targeting B7-H3, an immunoregulatory protein overexpressed in cancer cells, could help treat solid tumors, with fewer off-target toxicities and stronger therapeutic efficacy than previous ADCs with the same target and pyrrolobenzodiazepine (PBD) cytotoxic payload.

Optimization of the heavy chain and linker region of a previously developed B7-H3 ADC yielded a compound with Fc domain mutations, which was then conjugated to a PDB dimer payload via a modified PEG side chain. The resulting compound decreased the viability of B7-H3-positive embryonic kidney, colon cancer, and melanoma cell lines with IC50s in the low picomolar range. ...