This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SCH 717454 is a fully human anti-IGF-1R monoclonal antibody of the Immunoglobulin G1 (IgG1)/kappa isotype that binds the extra cellular portion of the human IGF-1R with high affinity. SCH 717454 inhibits IGF ligand binding, IGF-stimulated receptor phosphorylation, and human tumor cell proliferation. In addition to its activity in blocking IGF binding and receptor activation, SCH 717454 also induces IGF-1R degradation, and unlike some other IGF-1R directed antibodies, can induce tumor cell killing through an antibody-directed cellular cytotoxicity (ADCC) mechanism. Since SCH 717454 is known to decrease tumor cell proliferation in preclinical studies, analysis of the tumor specimens may provide direct information as to the biological effect of SCH 717454 in patients with osteosarcoma. The biology of osteosarcoma and Ewing sarcoma suggests that IGF-1R signaling may be an important mediator of the pathophysiology of these two tumors. The protocol aims to determine tumor cell proliferation response after dosing with SCH 717454 in subjects with resectable osteosarcoma that has relapsed after standard systemic therapy compared to the subject''s historical tumor cell proliferation as well as determine response rate in subjects with unresectable osteosarcoma and in subjects with refractory Ewing sarcoma. SCH 717454 will have antitumor activity in osteosarcoma and Ewing s sarcoma. SCH 717454 will decrease tumor cell proliferation in patient s with osteosarcoma.
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