ArticleCancer medicine2020
Improved targeting of an anti-TAG-72 antibody drug conjugate for the treatment of ovarian cancer.
Article in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Evaluation of [Molecules (Basel, Switzerland) · 2021Trial
- Increased longevity of circulating human IgG in an NSG Fc gamma receptor-1 deficient humanized mouse model.Journal of pharmaceutical sciences · 2025Article
- Development and Potent Anti-Tumor Activity of a Fully Humanized Anti-TAG-72-IL-2 Fusion Protein for Therapy of Solid Tumors.Cancers · 2025Article
- Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment.Frontiers in drug delivery · 2024Review
- Sialyl-Tn glycan epitope as a target for pancreatic cancer therapies.Frontiers in oncology · 2024Article
- Engineering T cell receptor fusion proteins using nonviral CRISPR/Cas9 genome editing for cancer immunotherapy.Bioengineering & translational medicine · 2023Article
- Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer.Archivum immunologiae et therapiae experimentalis · 2023Review
- Review
- CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies.Frontiers in immunology · 2023Review
- Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors.Journal for immunotherapy of cancer · 2022Article
- Review
- Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment.Frontiers in immunology · 2022Review
- Improved targeting of an anti-TAG-72 antibody drug conjugate for the treatment of ovarian cancer.Cancer medicine · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
introductionOvarian cancer has only a 17% 5-year survival rate in patients diagnosed with late stage disease. Tumor-associated glycoprotein-72 (TAG72), expressed in 88% of all stages of ovarian cancer, is an excellent candidate for antibody-targeted therapy, as it is not expressed in normal human adult tissues, except in the secretory endometrium.
methodsUsing the clinically relevant anti-TAG72 murine monoclonal antibody CC49, we evaluated antibody drug conjugates (ADCs) incorporating the highly potent, synthetic antimitotic agent monomethylauristatin E (MMAE). MMAE was conjugated to CC49 via reduced disulfides in the hinge region, using three different types of linker chemistry, vinylsulfone (VS-MMAE), bromoacetamido (Br-MMAE), and maleimido (mal-MMAE).
resultsThe drug antibody ratios (DARs) of the three ADCs were 2.3 for VS-MMAE, 10 for Br-MMAE, and 9.5 for mal-MMAE. All three ADCs exhibited excellent tumor to blood ratios on PET imaging, but the absolute uptake of CC49-mal-MMAE (3.3%ID/g) was low compared to CC49-Br-MMAE (6.43%ID/g), at 142 hours. Blood clearance at 43 hours was 38% for intact CC49, about 24% for both CC49-VS-MMAE and CC49-Br-MMAE, and 7% for CC49-mal-MMAE. CC49-VS-MMAE was not further studied due to its low DAR, while CC49-mal-MMAE was ineffective in the OVCAR3 xenograft likely due to its rapid blood clearance. In contrast, CC49-Br-MMAE treated mice exhibited an average of a 15.6 day tumor growth delay and a 40% increase in survival vs controls with four doses of 7.5 or 15 mg/kg of CC49-Br-MMAE.
conclusionWe conclude that CC49-Br-MMAE with a high DAR and stable linker performs well in a difficult to treat solid tumor model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.