A5043569662- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Glycosylation and Glycoproteins Research
- Medical Imaging Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Cancer Research and Treatments
- Lung Cancer Treatments and Mutations
- Medical Imaging and Pathology Studies
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Macrophage Migration Inhibitory Factor
- Synthesis and Biological Evaluation
- Colorectal Cancer Treatments and Studies
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Click Chemistry and Applications
- Thyroid Cancer Diagnosis and Treatment
- Advanced Radiotherapy Techniques
- Nanoparticle-Based Drug Delivery
- Pancreatic and Hepatic Oncology Research
Immunomedics (United States)
2012-2024
Gilead Sciences (United States)
2021-2024
Immunomedics (Germany)
2015-2024
Center for Molecular Medicine and Immunology
2009-2023
University of Colorado Denver
2017
Georgetown University
2017
University of Colorado Cancer Center
2017
Fox Chase Cancer Center
2011-2017
Dana-Farber Cancer Institute
2017
Indiana University Health
2017
Standard chemotherapy is associated with low response rates and short progression-free survival among patients pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), SN-38, conjugated to antibody by cleavable linker. enables delivery of high concentrations SN-38 tumors.
// David M. Goldenberg 1 , Thomas Cardillo Serengulam V. Govindan Edmund A. Rossi Robert Sharkey Immunomedics, Inc., Morris Plains, NJ, USA * Presented in part as a lecture by DMG, “Challenging the Dogmas: Clinical Efficacy of SN-38-conjugated Antibodies Solid Tumors,” at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapy, Barcelona, Spain, November 20, 2014. Correspondence to: Goldenberg, e-mail: dmg.gscancer@att.net Keywords: antibody-drug...
Small biomolecules are typically radiolabeled with <sup>18</sup>F by binding it to a carbon atom, process that usually is designed uniquely for each new molecule and requires several steps hours produce. We report facile method wherein first attached aluminum as Al<sup>18</sup>F, which then bound chelate peptide, forming stable Al<sup>18</sup>F-chelate-peptide complex in an efficient 1-pot process. <b>Methods:</b> For proof of principle, this was applied peptide suitable use bispecific...
Purpose Trop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an conjugate, targets Trop-2 the selective delivery of SN-38, active metabolite irinotecan. Patients and Methods We evaluated sacituzumab govitecan single-arm, multicenter trial patients with relapsed/refractory metastatic TNBC who received 10 mg/kg starting dose on days 1 8 21-day repeated cycles. The primary end points were safety...
Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite irinotecan. This phase I trial evaluated this ADC as potential therapeutic pretreated patients with variety metastatic solid cancers.Sacituzumab was administered days 1 and 8 21-day cycles, cycles repeated until dose-limiting toxicity or progression. Dose escalation followed standard 3 + scheme 4...
Evaluate the efficacy of an SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice monkeys, latter with tissue cross-reactivity hRS7 similar humans.
Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) made from a humanized anti-Trop-2 monoclonal antibody (hRS7) conjugated with the active metabolite of irinotecan, SN-38. In addition to its further characterization, as clinical utility IMMU-132 expands ever-widening range Trop-2-expressing solid tumor types, efficacy in new disease models needs be explored nonclinical setting. Unlike most ADCs that use ultratoxic drugs and stable linkers, uses moderately toxic drug...
Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in phase I/II multicenter trial (NCT01631552) patients with advanced epithelial cancers. This report summarizes the safety data from overall population (OSP) data, including additional disease cohorts not published previously.Patients refractory metastatic cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1...
BACKGROUND Sacituzumab govitecan (IMMU‐132), an antitrophoblastic cell‐surface antigen (anti‐Trop‐2) humanized antibody‐SN‐38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines pharmacokinetics and safety of multiple cycles IMMU‐132 at doses 8 or 10 mg/kg patients with diverse advanced epithelial cancers. METHODS Patients who prior therapies received on days 21‐day treatment cycles. Trop‐2 staining archived tumor specimens, clearance its...
No effective therapy is currently available for the management of patients with metastatic medullary thyroid carcinoma (MTC). The efficacy pretargeted radioimmunotherapy (pRAIT) bispecific monoclonal antibody (BsMAb) and a iodine-131 (131I) -labeled bivalent hapten evaluated.Twenty-nine advanced, progressive MTC, as documented by short serum calcitonin doubling times (Ct DTs), received an anti-carcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA) -indium BsMAb,...
Journal Article Carcinoembryonic Antigen in Histopathology: Immunoperoxidase Staining of Conventional Tissue Sections Get access David M. Goldenberg, Goldenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert Sharkey, Sharkey F. James Primus JNCI: the National Cancer Institute, Volume 57, Issue 1, July 1976, Pages 11–22, https://doi.org/10.1093/jnci/57.1.11 Published: 01 1976 history Received: 22 September 1975 Accepted: 06 January
We describe a platform technology, termed the dock and lock method, which uses natural binding between regulatory subunits of cAMP-dependent protein kinase anchoring domains A anchor proteins for general application in constructing bioactive conjugates different nonprotein molecules from modular on demand. This approach could allow quantitative site-specific coupling many biological substances diverse medical applications. The method is validated herein by producing bispecific,...
Several methods have been developed to label peptides with <sup>18</sup>F. However, in general these are laborious and require a multistep synthesis. We present facile method based on the chelation of <sup>18</sup>F-aluminum fluoride (Al<sup>18</sup>F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The is characterized labeling NOTA-octreotide (NOTA-d-Phe-<i>cyclo</i>[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH<sup>+</sup> 1305) [IMP466]) <b>Methods:</b> Octreotide was conjugated NOTA...
Sixteen patients with non-Hodgkin's lymphoma were infused 6.2 to 58.2 mCi (0.2 3.9 mg) doses of radioactive iodine (131I)-labeled LL2 immunoglobulin G (IgG) or F(ab')2, in order study antibody distribution, pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. is a murine IgG2a monoclonal (MAb) reactive B cells B-cell lymphoma. In series five assessable therapy patients, as small 30 131I-LL2 IgG F(ab')2 resulted responses (two partial remissions, two mixed minor responses, one...
We reported previously the feasibility to radiolabel peptides with fluorine-18 (18F) using a rapid one-pot method that first mixes 18F− Al3+ and then binds (Al18F)2+ complex NOTA ligand on peptide. In this report, we examined several new ligands determined how temperature, reaction time, reagent concentration affected radiolabeling yield. Four structural variations of had isolated yields ranging from 5.8% 87% under similar conditions. All Al18F complexes were stable in vitro human serum,...
The 3-step, unlabeled antibody, immunoperoxidase method for staining CEA in conventional histopathology sections was used to evaluate the presence of 950 different specimens, vast majority which were available as paraffin-embedded tissues fixed formalin. sensitivity clearly discriminated between normal or nonmalignant, diseased and neoplasms having increased quantities CEA. Thus, tumors epithelial origin, particularly adenocarcinomas squamous cell carcinomas gastrointestinal tract, bronchus,...
Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) non–small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), Trop-2 ADC, the targeting of SN-38. Patients and Methods evaluated IMMU-132 single-arm multicenter trial patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 21-day cycles. The primary end points were safety objective response rate (ORR). Progression-free survival overall...
The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. organofluoroaluminates easily accessible from reaction 1 AlF(3). X-ray diffraction studies revealed aluminum at center slightly distorted octahedron, fluorine occupying one axial positions. tert-butyl protected prochelator 7,...
This study examined the delivery of SN-38 to Trop-2-expressing tumors and assessed constitutive products in serum, liver, small intestine nude mice bearing human tumor xenografts (Capan-1 or NCI-N87) given a single injection irinotecan (40 mg/kg; ∼ 0.8 mg/mouse, containing 460 μg equivalents) sacituzumab govitecan (IMMU-132), an antibody-drug conjugate composed humanized anti-Trop-2 IgG coupled site specifically with average 7.6 molecules SN-38.At select times, tissues were extracted...
Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied patients pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and of 21-day cycles. The primary endpoints were safety objective response rate (ORR); duration response, progression-free survival (PFS), overall (OS) secondary endpoints.Results: Sixty percent showed tumor...