ArticleCancer medicine2019
Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C-Lock linker.
Article in Cancer medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Chemotherapeutic Drug-Antibody Conjugates (ChemoBodies): Recent Advances and Future Directions.Current oncology reports · 2025Review
- Unsaturated Phosphine Oxides for Modular Antibody Rebridging and Single Reagent Peptide-Cyclization-Bioconjugation.Angewandte Chemie (International ed. in English) · 2025Article
- Antibody-drug conjugate: a newly developed biological missile for tumor treatment.Frontiers in oncology · 2025Review
- Antibody-drug conjugates in gastric cancer: from molecular landscape to clinical strategies.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Review
- Chemo- and regio-selective differential modification of native cysteines on an antibodyChemical science · 2024Article
- Homogeneous multi-payload antibody-drug conjugates.Nature chemistry · 2024Review
- Bioorthogonal site-selective conjugation of fluorescent dyes to antibodies: method and potential applications.RSC advances · 2022Article
- A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Antibody-Drug Conjugates Containing Payloads from Marine Origin.Marine drugs · 2022Review
- Increasing the Potential of the Auristatin Cancer-Drug Family by Shifting the Conformational Equilibrium.Molecular pharmaceutics · 2019Article
- Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C-Lock linker.Cancer medicine · 2019Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) belong to a promising class of biopharmaceuticals in which target-killing of tumor cells was achieved by marrying the potency of the cytotoxic payload with the tumor specificity of the antibody. Here we developed a novel ADC (ZV0508) that targets 5T4 oncofetal antigen, which is overexpressed in many carcinomas on both bulk tumor cells and cancer stem cells. A novel cytotoxic payload called Duostatin-5 (Duo-5) which was derived from monomethyl auristatin F (MMAF) was attached to a 5T4 targeting antibody (ZV05) by interchain cysteine cross-linking conjugation via a disubstituted C-Lock linker. We have investigated the antitumor efficacy of ZV0508 by in vitro and in vivo studies, and compared its antitumor activity with ZV05-mcMMAF (ZV0501), in which MMAF was linked via a conventional noncleavable maleimidocaproyl linker. As results, ZV0508 exhibited ideal antiproliferative effects through blocking cell cycle and inducing cell apoptosis. The in vivo studies revealed that both ZV0501 and ZV0508 exhibited excellent antitumor activities even at a single dose. Although ZV0508 was inferior to ZV0501 in vitro, it elicited more durable antitumor responses than ZV0501 in vivo. The superior in vivo activity of ZV0508 may be due to the combined use of the disubstituted C-Lock linker and the novel payload Duo-5, resulting in a more stable and potent ADC. Taken together, these data suggest ZV0508 is a worthy candidate for the treatment of 5T4 positive cancers.
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