ArticleScientific reports2025
Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer.Translational lung cancer research · 2026Review
- Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Identification of antibody-drug conjugate payloads that are substrates of ATP-binding cassette drug efflux transporters.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Characterization of TROP-2 bispecific T cell engagers for immunotherapy of triple negative breast and bladder cancer.Frontiers in immunology · 2026Article
- Preclinical Pharmacokinetic, Pharmacodynamic, and Safety Profile of OBI-992: A Novel TROP2-Targeted Antibody-Drug Conjugate.Molecular cancer therapeutics · 2025Article
- Antibody-Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies.Biomedicines · 2025Review
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Authors and funding
15 authors.
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Abstract
Trophoblast cell surface antigen 2 (TROP2), a transmembrane glycoprotein highly expressed in a variety of epithelial cancers, has been considered as a primary therapeutic target for the development of antibody-drug conjugates (ADCs). OBI-992, an investigational TROP2-targeted ADC, is composed of a novel TROP2 antibody (R4702) conjugated to the topoisomerase I (TOP1) inhibitor exatecan through a hydrophilic enzyme-cleavable linker. This study aimed to characterize R4702 and OBI-992 in vitro. TROP2-targeted antibodies sacituzumab and datopotamab were employed as the comparators for R4702. ADCs sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) were used as benchmarks for OBI-992. Results revealed that R4702 binds to an epitope that is distinct from sacituzumab and datopotamab. The cytotoxicity of the OBI-992, SG, and Dato-DXd against different cancer cells is comparable despite they have different internalization profile. Upregulation of breast cancer resistance protein (BCRP) was observed in SG-resistant and Dato-DXd-resistant cells, but not in OBI-992-resistant cells. In addition, significant downregulation of TROP2 expression was detected with Dato-DXd-resistant cells and only slightly downregulation with SG- and OBI-992-resistant cells was observed. Moreover, substantial enhancement of cytotoxicity and DNA damage was found in the combination of OBI-992 with a poly (ADP-ribose) polymerase (PARP) inhibitor (talazoparib). Taken together, the findings in this study support further clinical development of OBI-992.
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