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49 results for “Antibody-Drug Conjugate”
Data for: A cell surface-binding antibody atlas nominates a MUC18-directed antibody-drug conjugate for targeting melanoma
<p><span>Recent advances in targeted therapy and immunotherapy have substantially improved the treatment of melanoma. However, therapeutic strategies are still needed for unresponsive or treatment-relapsed melanoma patients. To discover antibody-drug conjugate (ADC)-tractable cell surface targets for melanoma, we developed an atlas of melanoma cell surface binding antibodies (pAbs) using a proteome-scale antibody array platform (PETAL). Target identification of pAbs led to development of melanoma cell killing ADCs against LGR6, TRPM1, ASAP1, and MUC18, among others. MUC18 was overexpressed in both tumor cells and tumor-infiltrating blood vessels across major melanoma subtypes, making it a potential dual-compartment and universal melanoma therapeutic target. AMT-253, an MUC18-directed ADC based on topoisomerase I inhibitor exatecan and a self-immolative T moiety, had a higher therapeutic index compared to its microtubule inhibitor-based counterpart and favorable pharmacokinetics and tolerability in monkeys. AMT-253 exhibited MUC18-specific cytotoxicity through DNA damage and apoptosis and a strong bystander killing effect, leading to potent antitumor activities against melanoma cell line and patient-derived xenograft models. Tumor vasculature-targeting by a mouse MUC18-specific antibody-T1000-exatecan conjugate inhibited tumor growth in human melanoma xenografts. Combination therapy of AMT-253 with an anti-angiogenic agent generated higher efficacy than single agent in a mucosal melanoma model. Beyond melanoma, AMT-253 was also efficacious in a wide range of MUC18-expressing solid tumors. Efficient target/antibody discovery in combination with the T moiety-exatecan linker-payload exemplified here may facilitate discovery of new ADC to improve cancer treatment</span><span>.</span></p>
Data for: A cell surface-binding antibody atlas nominates a MUC18-directed antibody-drug conjugate for targeting melanoma
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ADCE-T02, a Tissue Factor Targeted Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours
ClinicalTrials.gov study NCT06597721. IPD Sharing: Not stated. Countries: 2. Publications: 0.
Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer
ClinicalTrials.gov study NCT05652868. IPD Sharing: YES. Countries: 7. Publications: 1.
First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients
ClinicalTrials.gov study NCT02277717. IPD Sharing: UNDECIDED. Countries: 4. Publications: 2.
A Window-of-opportunity Study of U3-1402, a HER3-targeting Antibody-drug Conjugate in Operable Breast Cancer According to ERBB3 Expression
ClinicalTrials.gov study NCT04610528. IPD Sharing: NO. Countries: 1. Publications: 1.
A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma
ClinicalTrials.gov study NCT01101594. IPD Sharing: Not stated. Countries: 1. Publications: 8.
A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate BYON3521
ClinicalTrials.gov study NCT05323045. IPD Sharing: NO. Countries: 4. Publications: 1.
Data from: Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer
Antibodies are widely available and cost-effective research tools in life science, and antibody conjugates are now extensively used for targeted therapy, immunohistochemical staining, or in vivo diagnostic imaging of cancer. Significant advances in site-specific antibody labeling technologies have enabled the production of highly characterized and homogenous conjugates for biomedical purposes, and some recent studies have utilized site-specific labeling to synthesize bifunctional antibody conjugates with both imaging and drug delivery properties. While these advances are important for the clinical safety and efficacy of such biologics, these techniques can also be difficult, expensive, and time-consuming. Furthermore, antibody-drug conjugates (ADCs) used for tumor treatment generally remain distinct from conjugates used for diagnosis. Thus, there exists a need to develop simple dual-labeling methods for efficient therapeutic and diagnostic evaluation of antibody conjugates in pre-clinical model systems. Here, we present a rapid and simple method utilizing commercially available reagents for synthesizing a dual-labeled fluorescent ADC. Further, we demonstrate the fluorescent ADC's utility for simultaneous targeted therapy and molecular imaging of cancer both in vitro and in vivo. Employing non-site-specific, amine-reactive chemistry, our novel biopharmaceutical theranostic is a monoclonal antibody specific for a carcinoembryonic antigen (CEA) biomarker conjugated to both paclitaxel and a near-infrared (NIR), polyethylene glycol modified (PEGylated) fluorophore (DyLight™ 680-4xPEG). Using in vitro systems, we demonstrate that this fluorescent ADC selectively binds a CEA-positive pancreatic cancer cell line (BxPC-3) in immunofluorescent staining and flow cytometry, exhibits efficient internalization kinetics, and is cytotoxic. Model studies using a xenograft of BxPC-3 cells in athymic mice also show the fluorescent ADC's efficacy in detecting tumors in vivo and inhibiting tumor growth more effectively than equimolar amounts of unconjugated drug. Overall, our results demonstrate that non-selective, amine-targeting chemistry is an effective dual-labeling method for synthesizing and evaluating a bifunctional fluorescent antibody-drug conjugate, allowing concurrent detection, monitoring and treatment of cancer.
Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Adult Patients With Mesenchymal Epithelial Transition Factor (MET) Overexpressing Advanced Cancer
ClinicalTrials.gov study NCT04982224. IPD Sharing: YES. Countries: 1. Publications: 0.
To Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-drug Conjugate, GSK2857916 Administered in Combination With Lenalidomide Plus Dexamethasone (Arm A), or in Combination With Bort
ClinicalTrials.gov study NCT03544281. IPD Sharing: NO. Countries: 5. Publications: 0.
Data from: Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer
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MUC1-C DEPENDENCY IN DRUG RESISTANT HR+/HER2- BREAST CANCER IDENTIFIES A NEW TARGET FOR TREATMENT WITH AN ANTIBODY-DRUG CONJUGATE
GEO Series GSE272989. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Tumor-derived biomarkers beyond antigen expression enhance efficacy of CD276/B7H3 antibody-drug conjugate in metastatic prostate cancer
GEO Series GSE236808. Homo sapiens. 67 samples. Type: Expression profiling by high throughput sequencing.
A microbial-inspired antibody-drug conjugate for cancer immunotherapy
GEO Series GSE255937. Mus musculus. 1 samples. Type: Expression profiling by high throughput sequencing.
ABBV-319: A First-In-Class CD19-targeting Glucocorticoid Receptor Modulator (GRM) Agonist Antibody-Drug Conjugate (ADC) for the Treatment of B-cell Malignancies [RNA-seq]
GEO Series GSE249023. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Combined therapy with DR5- targeting antibody-drug conjugate and CDK inhibitors as a novel strategy for advanced MSS and MSI-H colorectal cancer
GEO Series GSE289746. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Identification of MUC1-C Dependence in Drug-Resistant Advanced Prostate Cancer Uncovers a New Target for Antibody-Drug Conjugate Therapy
GEO Series GSE276890. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Identification of MUC1-C Dependence in Drug-Resistant Advanced Prostate Cancer Uncovers a New Target for Antibody-Drug Conjugate Therapy
GEO Series GSE276750. Homo sapiens. 6 samples. Type: Expression profiling by high throughput sequencing.
Development of antibody-drug conjugates targeting L1CAM to treat metastatic cancer
GEO Series GSE307811. Homo sapiens. 1 samples. Type: Expression profiling by high throughput sequencing.
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International Brain Laboratory public data
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OpenNeuro
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