CDR GRAFTED ANTIBODY FOR RADIOIMMUNOTHERAPY OF LYMPHOMA

用于淋巴瘤放射免疫治疗的 CDR 移植抗体

• 批准号: 2109699
• 负责人: GARY Leonard GRIFFITHS
• 金额: $ 10万
• 依托单位: IMMUNOMEDICS, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-10 至 1995-09-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2109699
• 关键词: Animalia; differentiation antigens; immunoconjugates; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy; nonHodgkin's lymphoma; nonhuman therapy evaluation; radiochemistry; radiotracer; yttrium

DESCRIPTION: (Adapted from the applicant's abstract) This Phase I research will test the hypothesis that an optimum, commercially viable radioimmunotherapy agent is a Y-90-radiolabeled cdr-grafted LL2 MAb, targeted against radiosensitive Non-Hodgkin's lymphoma. Y-90 is to be used because of its desirable radiophysical properties, possible use on an out-patient basis and commercial availability, while the cdr-grafted MAb has been selected in order to minimize human anti-mouse antibody response, which could preclude repeat treatment. Conjugates will be radiolabeled using a bifunctional chelate based on 2-benzyl-DTPA, since routine labeling can be performed in 93- 98 percent incorporation yields within l hour. Y-90-labeled cdr-grafted LL2 will be compared to Y-90 radiolabeled murine LL2 and to the corresponding radioiodinated antibodies for stability; in in vitro cell-binding, internalization and isotope cellular retention studies, and in vivo in animal tumor xenograft models. At the conclusion of the Phase I period, the investigators will have either confirmed the suitability of the Y-90- labeled cdr-grafted LL2 for radioimmunotherapy or decided that one of the other agents would be preferred, based on the combined cell processing and tumor targeting studies. The final goal is a clinically efficacious, commercially useful, radioimmunotherapy product.

描述：（根据申请人的摘要进行了改编）此阶段I 研究将检验以下假设，即最佳，商业上可行 放射免疫治疗剂是Y-90-Radiolabele cdr-Grafted LL2 mAb， 针对放射敏感的非霍奇金淋巴瘤。 Y-90是 由于其理想的放射物理特性而使用，因此可能使用 门诊和商业可用性，而CDR-Grafted 已选择MAB以最大程度地减少人类抗小鼠抗体 反应，这可能排除重复治疗。 缀合物会 使用基于2-苯乙基DTPA的双功能性螯合物进行放射性标记，因为 常规标签可以以93％至98％的合并产量进行 在L小时内。 将Y-90标记的CDR-GRAFTed LL2与Y-90进行比较 放射标记的鼠LL2，并与相应的放射性固定剂 稳定性的抗体；在体外细胞结合，内在化和 同位素细胞保留研究和动物肿瘤的体内 异种移植模型。 在第一阶段时期结束时， 调查人员将确认Y-90-的适用性 标记为放射免疫疗法的CDR-Grafted LL2或决定之一 基于组合细胞，其他代理将是优选的 加工和肿瘤靶向研究。 最终目标是临床 有效的，商业上有用的放射免疫疗法产品。