Molecular Design and Preclinical Evaluation of GenSci143, a Novel B7-H3- and PSMA-Directed Bispecific Antibody-Drug Conjugate, for the Treatment of Prostate Cancer - PubMed
4 hours ago
- #Bispecific ADC
- #Prostate Cancer Therapy
- #Antigen Heterogeneity
- GenSci143 is a novel bispecific antibody-drug conjugate (BsADC) targeting both B7-H3 and PSMA for treating metastatic castration-resistant prostate cancer (mCRPC).
- It is designed to overcome tumor antigen heterogeneity and associated drug resistance by dual targeting, with high co-expression of B7-H3 and PSMA in prostate cancer supporting this strategy.
- The ADC features a highly active topoisomerase 1 inhibitor payload, a plasma-stable linker to minimize off-target toxicity, and shows strong binding, internalization, and cytotoxicity in vitro, including a robust bystander killing effect.
- In preclinical studies using cancer cell line-derived and patient-derived xenograft models, GenSci143 induced profound tumor regression and demonstrated superior antitumor activity compared to competitor ADCs.
- GenSci143 exhibited excellent plasma stability and favorable pharmacokinetic properties in non-human primates, indicating translational relevance and supporting its clinical development as a promising therapeutic candidate.