MABS TO HUMAN SARCOMA FOR DIAGNOSIS AND TREATMENT

MABS 用于人类肉瘤的诊断和治疗

• 批准号: 3201497
• 负责人: TAPAS K. DAS GUPTA
• 金额: $ 13.79万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3201497
• 关键词: SDS polyacrylamide gel electrophoresis; antibody formation; athymic mouse; cell line; cell mediated cytotoxicity; cytotoxicity; diagnosis design /evaluation; flow cytometry; glycoproteins; histochemistry /cytochemistry; human tissue; hybridomas; immunocytochemistry; immunologic techniques; immunopathology; immunoprecipitation; laboratory mouse; lectin; membrane proteins; mesenchyme; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplastic transformation; osteosarcoma; radioimmunoassay; sarcoma; tissue /cell culture; tumor antigens

Approximately 5000 new cases of soft tissue sarcoma are diagnosed yearly. Because of their relatively low incidence these extremely malignant tumors which arise in extraskeletal mesenchymal derived tissues have almost assumed "orphan" status in the explosive development of monoclonal antibodies (MAbs) to carcinoma cell surface associated antigens. Our laboratory has generated a series of MAbs to sarcoma related antigens which have been useful in the diagnosis of this diverse group of tumors. Characterization of MAbs generated by lectin selection of sarcoma membrane associated antigens has improved upon this series by producing a second generation of high affinity MAbs with an improved specificity for sarcoma membrane associated glycoproteins (antigens). Our specific aims are 1) select subgroups of MAbs that show broad sarcoma specificity, sarcoma subtype specificity, and affinity for shed antigens using membrane preparations of fresh surgical tissues, cultured cells, tissue sections and biochemically characterized antigens, 2) use an immunocytochemical approach to identify whether a MAb selected on the basis of RIA has a utility in aiding pathologic diagnosis, 3) expand upon the immunocytochemical approach and use selected MAbs to examine cytoxicity in vitro and in athymic mice with conjugates to a model drug an toxin. Our long term goal continues to be to secure antibodies that will improve our understanding of mesenchymal cell transformation and have a significant clinical impact in the pathological diagnosis, clinical diagnosis and therapy of soft tissue sarcoma(s).

每年诊断出约5000例软组织肉瘤病例。 由于它们的发病率相对较低 在骨架外间充质衍生组织中产生的肿瘤具有 单克隆的爆炸性发展中几乎假定的“孤儿”状态 与癌细胞表面相关抗原的抗体（mAb）。 我们的 实验室已经为肉瘤相关的抗原产生了一系列mABS 这在诊断这一多种肿瘤的诊断中很有用。 通过选择肉瘤的凝集素选择产生的mAb的表征 膜相关的抗原通过产生A 第二代高亲和力mAB具有提高特异性 肉瘤膜相关糖蛋白（抗原）。 我们的具体目标 是1）选择显示广泛肉瘤特异性的mAb的子组， 肉瘤亚型特异性，以及使用使用的抗原的亲和力 新鲜手术组织，培养细胞，组织的膜制剂 部分和生化特征抗原，2）使用 免疫细胞化学方法可以确定在 RIA的基础具有帮助病理学诊断的实用性，3）扩展 免疫细胞化学方法并使用选定的mAB检查 体外的细胞毒性和与偶联物与模型药物的无性小鼠中的细胞毒性 毒素。 我们的长期目标继续是确保将改善的抗体 我们对间充质细胞转化的理解，并具有 病理诊断，临床的重大临床影响 软组织肉瘤的诊断和治疗。