ArticleMolecular cancer therapeutics2024
FZ-AD005, a Novel DLL3-Targeted Antibody-Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models.
Article in Molecular cancer therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.Drugs · 2026Review
- Structure-based design and optimization of cyclic peptide ligands targeting delta-like ligand 3.RSC advances · 2026Article
- Updates on Antibody Drug Conjugates and Bispecific T-Cell Engagers in SCLC.Antibodies (Basel, Switzerland) · 2026Review
- Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Comparative Enzymatic and Stability Assays Reveal GPLG as an Effective Cathepsin B Cleavable Linker for Tumor-Targeting Drug Conjugates.ACS omega · 2025Article
- What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?JTO clinical and research reports · 2025Review
- SC134-deruxtecan, a fucosyl-GM1 targeting ADC for small cell lung cancer therapy.Journal of translational medicine · 2025Article
- ADCNet: a unified framework for predicting the activity of antibody-drug conjugates.Briefings in bioinformatics · 2025Article
- Targeting DLL3: Innovative Strategies for Tumor Treatment.Pharmaceutics · 2025Review
- Harnessing delta-like ligand 3: bridging biomarker discovery to next-generation immunotherapies in refractory small cell lung cancer.Frontiers in immunology · 2025Review
- Advances in adoptive cell therapies in small cell lung cancer.Exploration of targeted anti-tumor therapy · 2025Review
- Intratumoral heterogeneity and potential treatment strategies in small cell lung cancer.Frontiers in oncology · 2025Review
- Expanding the immunotherapy universe in extensive-stage small cell lung cancer: from chemoimmunotherapy backbone to next-wave combinations.Frontiers in immunology · 2025Review
- Emerging Nanomedicine Approaches in Targeted Lung Cancer Treatment.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delta-like ligand 3 (DLL3) is overexpressed in small cell lung cancer (SCLC) and has been considered an attractive target for SCLC therapy. Rovalpituzumab tesirine was the first DLL3-targeted antibody-drug conjugate (ADC) to enter clinical studies. However, serious adverse events limited progress in the treatment of SCLC with rovalpituzumab tesirine. In this study, we developed a novel DLL3-targeted ADC, FZ-AD005, by using DXd with potent cytotoxicity and a relatively better safety profile to maximize the therapeutic index. FZ-AD005 was generated by a novel anti-DLL3 antibody, FZ-A038, and a valine-alanine (Val-Ala) dipeptide linker to conjugate DXd. Moreover, Fc-silencing technology was introduced in FZ-AD005 to avoid off-target toxicity mediated by FcγRs and showed negligible Fc-mediated effector functions in vitro. In preclinical evaluation, FZ-AD005 exhibited DLL3-specific binding and demonstrated efficient internalization, bystander killing, and excellent in vivo antitumor activities in cell line-derived xenograft and patient-derived xenograft models. FZ-AD005 was stable in circulation with acceptable pharmacokinetic profiles in cynomolgus monkeys. FZ-AD005 was well tolerated in rats and monkeys. The safety profile of FZ-AD005 was favorable, and the highest nonseverely toxic dose was 30 mg/kg in cynomolgus monkeys. In conclusion, FZ-AD005 has the potential to be a superior DLL3-targeted ADC with a wide therapeutic window and is expected to provide clinical benefits for the treatment of patients with SCLC.
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