A STUDY TO DETERMINE THE ACTIVITY OF SCH717454 IN SUBJECTS WITH OSTEOSARCOMA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 SCH 717454是一种免疫球蛋白G1（IgG 1）/κ同种型的全人源抗IGF-1 R单克隆抗体，可高亲和力结合人IGF-1 R的细胞外部分。SCH 717454抑制IGF配体结合、IGF刺激的受体磷酸化和人肿瘤细胞增殖。除了阻断IGF结合和受体活化的活性外，SCH 717454还诱导IGF-1 R降解，与其他一些IGF-1 R定向抗体不同，SCH 717454可通过抗体定向细胞毒性（ADCC）机制诱导肿瘤细胞杀伤。由于临床前研究中已知SCH 717454可降低肿瘤细胞增殖，因此肿瘤标本分析可提供SCH 717454在骨肉瘤患者中生物学效应的直接信息。骨肉瘤和尤文肉瘤的生物学表明，IGF-1 R信号可能是这两种肿瘤的病理生理学的重要介质。该方案旨在确定标准全身治疗后复发的可切除骨肉瘤受试者接受SCH 717454给药后的肿瘤细胞增殖应答，并与受试者的历史肿瘤细胞增殖进行比较，同时确定不可切除骨肉瘤受试者和难治性尤文肉瘤受试者的缓解率。 SCH 717454在骨肉瘤和尤文氏肉瘤中具有抗肿瘤活性。 SCH 717454可降低骨肉瘤患者的肿瘤细胞增殖。

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.