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tleonardo21: ope similar to nimotuzumab and a commercially available antibody, which recognized a cytoplasmic domain of EGFR. With mR3, there was a correlation between EGFR expression independent of localization and ErbB3 and MAPK expression, as well as...
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tleonardo21: adiation . For mAbbased therapies, the development of phagedisplay techniques and the creation of transgenic mice that encode the human IgG locus have resulted in the ability to isolate and test fully human mAbs as one strategy to address these...
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mazachariah83: tibodyderived agents, and small molecule inhibitors. Like cetuximab, nimotuzumab is constructed on an IgG1 framework that potentially allows these agents to mediate ADCC via natural killer cells and macrophages. Nimotuzumab binds to EGFR on...
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dbrendan88: derlie the development of two agents currently in clinical trial, the antiEGFR/antiErbB3 IgG MEHD7945A and the antiErbB2/antiErbB3 bispecific singlechain Fv MM111 . In contrast to other bsAbs that use distinct variable domains to bind to each...
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dbrendan88: were engineered to bind with high affinity to both EGFR and ErbB3 on nonhomologous epitopes . This dualspecificity IgG is capable of blocking liganddependent activation of both EGFR and ErbB3 and has preclinical activity against multiple EGFRdriven...
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wcolom7: hese areas may also increase clinical response. 2.3. Emerging ErbBfamily targeting agents Overcoming mechanisms of intrinsic and acquired resistance to current generation ErbBtargeted therapies is a critical area of investigation. Nextgeneration...
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mazachariah83: The clinical implications of this are unclear, given preclinical data that higher affinity antibodies can be associated with decreased tumor penetration . Preliminary clinical data with nimotuzumab indicate that it can be combined safely with...
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wcolom7: cking, or suboptimal immune modulation, as detailed in sections 3 and 4 of this article. Further, the ability of current dosing schedules to optimally inhibit EGFR ligand binding and downstream signaling without regard to tumor burden or receptor...
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mcemerson66: evels of immunogenicity and by extension better PK and PD profiles than their chimeric and humanized counterparts, leading to more effective tumor control. This class of agents is exemplified by the antiEGFR antibodies panitumumab , zalutumumab...
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stpeter51: hem with cetuximab as a monotherapy . They reported a response rate of 12.6%, disease control rate of 46% and median overall survival of 5.84 months. Overall, the singleagent activity of cetuximab among patients with platinum refractory SCCHN...
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coalbu93: was borne out in preclinical testing of two bsAbs, an IgGlike Didiabody that was generated from the variable domains of the antiEGFR IMC11F8 and antiIGF1R IMCA12 and an IgGscFv created from a human anti EGFR FAb and a stabilityenhanced variant...
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sglunz18: spective of therapy. This obviously needs to be studied further in a prospective fashion . Resistance may arise from activation of crucial signal transduction molecules downstream from EGFR, upregulation of other receptor tyrosine kinases that...
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gwilfredo16: n phase I clinical trials in the setting of SCCHN, pancreatic, colorectal and nonsmallcell lung cancers. The bsscFV MM111 uses human serum albumin as a linker between the anti ErbB2 and antiErbB3 scFv to improve the PK of the molecule. Analogous...
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mazachariah83: cancers have low cure rates even with induction chemotherapy or other forms of treatment intensification . Improved therapy for this second group of patients may depend on the development of novel agents that target the dysregulated signaling...
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mikennith65: in a majority of SCCHN, and is associated with inferior survival, radioresistance, and locoregional failure . Early preclinical studies revealed the antitumor effects of EGFRdirected monoclonal antibodies in epithelial cancer cell lines and...
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dprosonic99: l, 442 patients with advanced SCCHN who had not received prior treatment for recurrent/metastatic disease were randomized to either a platinumcontaining doublet or a similar doublet with cetuximab . The chemotherapy regimen used was platinum...
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