Search results for: Mouse Anti-Human c-met Antibodies
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#31924725 2020/01/10 To Up
Light-Induced Radiosynthesis of Zr-DFO-Azepin-Onartuzumab for Imaging the Hepatocyte Growth Factor Receptor.
Methods that provide rapid access to radiolabeled antibodies are vital in the development of diagnostic and radiotherapeutic agents for PET or radioimmunotherapy. The human hepatocyte growth factor receptor (c-MET) signaling pathway is dysregulated in several malignancies, including gastric cancer, and is an important biomarker in drug discovery. Here, we used a photoradiochemical approach to produce Zr-radiolabeled onartuzumab (a monovalent, antihuman c-MET antibody), starting directly from the fully formulated drug (MetMAb). Simultaneous Zr-radiolabeling and protein conjugation was performed in one-pot reactions containing Zr-oxalate, the photoactive chelate desferrioxamine B (DFO)-aryl azide (DFO-ArN), and MetMAb to give Zr-DFO-azepin-onartuzumab. As a control, Zr-DFO-benzyl Bn-isothiocyanate Bn-NCS-onartuzumab was prepared via a conventional two-step process using prepurified onartuzumab and DFO-Bn-NCS. Radiotracers were purified by using size-exclusion methods and evaluated by radiochromatography. Radiochemical stability was studied in human serum, and immunoreactivity was determined by cellular binding assays using MKN-45 gastric carcinoma cells. PET imaging at multiple time points (0-72 h) was performed on female athymic nude mice bearing subcutaneous MKN-45 xenografts. Biodistribution experiments were performed after the final image was obtained. The tumor specificity of Zr-DFO-azepin-onartuzumab was assessed in vivo by competitive inhibition (blocking) studies. Initial photoradiosynthesis experiments produced Zr-DFO-azepin-onartuzumab in less than 15 min, with an isolated decay-corrected radiochemical yield (RCY) of 24.8%, a radiochemical purity of approximately 90%, and a molar activity of approximately 1.5 MBq nmol Reaction optimization improved the radiochemical conversion of Zr-DFO-azepin-onartuzumab to 56.9% ± 4.1% ( = 3), with isolated RCYs of 41.2% ± 10.6% ( = 3) and radiochemical purity of more than 90%. Conventional methods produced Zr-DFO-Bn-NCS-onartuzumab with an isolated RCY of more than 97%, radiochemical purity of more than 97% and molar activity of approximately 14.0 MBq nmol Both radiotracers were immunoreactive and stable in human serum. PET imaging and biodistribution studies showed high tumor uptake for both radiotracers. By 72 h, tumor and liver uptake (percentage injected dose [%ID]) reached 15.37 ± 5.21 %ID g and 6.56 ± 4.03 %ID g, respectively, for Zr-DFO-azepin-onartuzumab ( = 4) and 21.38 ± 11.57 %ID g and 18.84 ± 6.03 %ID g, respectively, for Zr-DFO-Bn-NCS-onartuzumab ( = 4). Blocking experiments gave a statistically significant reduction in tumor uptake (6.34 ± 0.47 %ID g) of Zr-DFO-azepin-onartuzumab ( = 4). The experiments demonstrated that photoradiosynthesis is a viable alternative approach for producing Zr-radiolabeled antibodies directly in protein formulation buffer, reducing protein aggregation and liver uptake.Simon Klingler, Rachael Fay, Jason P Holland
2390 related Products with: Light-Induced Radiosynthesis of Zr-DFO-Azepin-Onartuzumab for Imaging the Hepatocyte Growth Factor Receptor.
20 ug2 Pieces/Box5 x 50 ug250ug10ug1 kit(96 Wells)2ug0.1 mg2ug5ug2ug x 2010ugRelated Pathways
#19825800 // To Up
Therapeutic potential of hepatocyte growth factor/scatter factor neutralizing antibodies: inhibition of tumor growth in both autocrine and paracrine hepatocyte growth factor/scatter factor:c-Met-driven models of leiomyosarcoma.
Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, have been implicated in the growth and progression of a variety of solid human tumors. Thus, inhibiting HGF/SF:c-Met signaling may provide a novel therapeutic approach for treating human tumors. We have generated and characterized fully human monoclonal antibodies that bind to and neutralize human HGF/SF. In this study, we tested the effects of the investigational, human anti-human HGF/SF monoclonal antibody, AMG 102, and a mixture of mouse anti-human HGF/SF monoclonal antibodies (Amix) on HGF/SF-mediated cell migration, proliferation, and invasion in vitro. Both agents had high HGF/SF-neutralizing activity in these cell-based assays. The HGF/SF:c-Met pathway has been implicated in the growth of sarcomas; thus, we also investigated the effect of AMG 102 on the growth of human leiomyosarcoma (SK-LMS-1) in HGF/SF transgenic C3H severe combined immunodeficient mice engineered to express high levels of human HGF/SF, as well as tumor growth of an autocrine variant of the SK-LMS-1 cell line (SK-LMS-1TO) in nude mice. The results indicate that interrupting autocrine and/or paracrine HGF/SF:c-Met signaling with AMG 102 has profound antitumor effects. These findings suggest that blocking HGF/SF:c-Met signaling may provide a potent intervention strategy to treat patients with HGF/SF:c-Met-dependent tumors.Chong-Feng Gao, Qian Xie, Yu-Wen Zhang, Yanli Su, Ping Zhao, Brian Cao, Kyle Furge, Jan Sun, Karen Rex, Tao Osgood, Angela Coxon, Teresa L Burgess, George F Vande Woude
1768 related Products with: Therapeutic potential of hepatocyte growth factor/scatter factor neutralizing antibodies: inhibition of tumor growth in both autocrine and paracrine hepatocyte growth factor/scatter factor:c-Met-driven models of leiomyosarcoma.
100.00 ug100.00 ug100.00 ug100 μg4 Membranes/Box100.00 ug100.00 ug100.00 ug2 Pieces/Box1 kit(96 Wells)10ug100.00 ugRelated Pathways
#19220580 2009/02/09 To Up
Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Vascular endothelial growth factor, platelet derived growth factor and the Raf/mitogen-activated protein kinase/extracellular signal regulated kinase (Raf/MEK/ERK) signalling pathway regulates the growth, neovascularization, invasiveness and metastatic potential of HCC. In this study, we investigated the in vivo antitumour activity and mechanisms of action of sorafenib tosylate on four patient-derived HCC xenografts. Sorafenib dosed at 50 mg/kg and 100 mg/kg inhibited tumour growth by 85% and 96%, respectively. Sorafenib-induced growth suppression and apoptosis were associated with inhibition of angiogenesis, down-regulation of phospho-platelet-derived growth factor receptor beta Tyr1021, phospho-eIF4E Ser209, phospho-c-Raf Ser259, c-Raf, Mcl-1, Bcl-2, Bcl-x and positive cell cycle regulators, up-regulation of apoptosis signalling kinase-1, p27 and p21. Expression of IGF-1Rbeta and phosphorylation of c-Raf Ser338, MEK1/2 Ser217/221 and ERK1/2 Thr202/Tyr204 were increased by sorafenib treatment. Phosphorylation of mammalian target-of-rapamycin (mTOR) targets (p70S6K, S6R and 4EBP1) was reduced by sorafenib in sorafenib-sensitive lines but activated in sorafenib-less-sensitive 10-0505 xenograft. Sorafenib-induced phosphorylation of c-met, p70S6K and 4EBP1 was significantly reduced when 10-0505 cells were co-treated with anti-human anti-HGF antibody, suggesting that treatment with sorafenib leads to increased HGF secretion and activation of c-met and mTOR targets. Treatment of 10-0505 tumours with sorafenib plus rapamycin resulted in growth inhibition, inhibition of vascular endothelial growth factor receptor-2 phosphorylation, increased apoptosis and completely blocked sorafenib-induced phosphorylation of mTOR targets and cyclin B1 expression. These data also provide a strong rationale for clinical investigation of sorafenib in combination with mTOR inhibitors in patients with HCC.Hung Huynh, Van Chanh Ngo, Heng Nung Koong, Donald Poon, Su Pin Choo, Choon Hua Thng, Pierce Chow, Hock Soo Ong, Alexander Chung, Khee Chee Soo
1568 related Products with: Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma.
10ug100.00 ug100 ul100.00 ug100.00 ug100.00 ugRelated Pathways
#15826299 2005/04/12 To Up
Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance.
The development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.Fariba Nayeri, Daniel Aili, Tayeb Nayeri, Junyang Xu, Sven Almer, Ingemar Lundström, Britt Akerlind, Bo Liedberg
2136 related Products with: Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance.
100.00 ug1 kit(96 Wells)0.1ml (1mg/ml)100.00 ug1 kit(96 Wells)100.00 ug10ug16 Arrays/Slide100.00 ug10ug100.00 ug4 Membranes/BoxRelated Pathways
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