ArticlePharmaceutical research2026
A Newly Designed Antibody-drug Conjugate Targeting B7-H3 Demonstrates Enhanced Therapeutic Efficacy Across a Spectrum of Cancers.
Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionThe development of antibody-drug conjugates (ADCs) has accelerated due to their tumor-targeting precision. However, challenges in optimizing the target-linker-payload combination often lead to attrition from safety or efficacy issues, highlighting the need for ADCs with an improved therapeutic index. This study presents a newly designed B7-H3-targeted ADC, BR112, and demonstrates its superior preclinical efficacy across multiple models.
methodsBR112 comprises a humanized anti-B7-H3 antibody (112-59) conjugated to the microtubule inhibitor MMAE via a Pyridazinedione-valine-citrulline-p-aminobenzyl (PD-VC-PAB) linker with a drug-to-antibody ratio (DAR) of 4.15. The binding affinity and internalization profile of 112-59 were evaluated across multiple cell lines. In vitro cytotoxicity and in vivo antitumor efficacy were assessed in multiple cancer cell lines and three xenograft models. Pharmacokinetics of BR112 were analyzed in cynomolgus monkeys.
resultsThe antibody 112-59 exhibited high binding affinity for human B7-H3 (Kd = 5.28 nM), with potent cell-binding (EC50 ≈ 1 nM) and superior internalization across multiple cancer cell lines, exceeding the performance of antibodies used in clinical-stage comparator ADCs (MGC018 and DS-7300). Consequently, BR112 demonstrated potent cytotoxicity in vitro, with IC50 values ranging from femtomolar to nanomolar. In vivo, BR112 induced complete tumor regression in xenograft models (HCC1954, HCC1806, Calu-6) at doses of 3-10 mg/kg, outperforming both MGC018 and DS-7300. Pharmacokinetic studies in cynomolgus monkeys showed dose-proportional exposure and minimal MMAE release, confirming linker stability.
conclusionThis study positions BR112 as a promising therapeutic candidate with enhanced efficacy and a stable pharmacokinetic profile for the treatment of B7-H3-expressing solid tumors.
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