A Newly Designed Antibody-drug Conjugate Targeting B7-H3 Demonstrates Enhanced Therapeutic Efficacy Across a Spectrum of Cancers - PubMed
5 hours ago
- #B7-H3
- #cancer therapy
- #antibody-drug conjugate
- A new antibody-drug conjugate (ADC) named BR112 targets B7-H3, showing enhanced therapeutic efficacy across various cancers.
- BR112 consists of a humanized anti-B7-H3 antibody conjugated to MMAE via a PD-VC-PAB linker with a DAR of 4.15.
- The antibody (112-59) exhibits high binding affinity (Kd = 5.28 nM), strong cell-binding, and superior internalization compared to clinical-stage ADCs like MGC018 and DS-7300.
- In vitro cytotoxicity of BR112 is potent, with IC50 values ranging from femtomolar to nanomolar.
- In vivo studies show complete tumor regression in xenograft models at doses of 3-10 mg/kg, outperforming comparator ADCs.
- Pharmacokinetic studies in cynomolgus monkeys indicate dose-proportional exposure and minimal MMAE release, confirming linker stability.