IMMUNOTOXIN PROTOCOLS

免疫毒素方案

• 批准号: 5201307
• 负责人: E SAUSVILLE
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201307
• 关键词: B lymphocyte; CD antigens; clinical trials; combination chemotherapy; dosage; human subject; immunoconjugates; immunoglobulin G; immunotoxicity; injection /infusion; lymphoma; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology

A. A Pilot Phase I Study of Combination Therapy with Continuous Infusion Immunotoxins IgG-RFB4-SMPT-dgA plus IgG-HD37-SMPT-dgA in Refractory CD19+, CD22+ B cell Lymphoma. This study builds on the prior experience with the respective immunotoxins utilized as single agents and seeks to determine the safety of the cocktail administered together as well as seeking to obtain some initial evidence of efficacy. Two dose levels(5 and 10 mg/M2/192 hr of each toxin have been thus far studied. There is initial evidence that the MTD will differ depending on whether circulating tumor cells are in evidence. Two of three patients without circulating tumor cells experienced Grade III toxicity at the higher dose level, whereas none of three patients with circulating tumor cells experienced Grade III toxicity or greater. Initial evidence has been obtained that in the same patient the handling of the immunotoxins differed depending on the expression of the target antigens. B. Correlative studies with Immunotoxins and Unconjugated Antibodies. In correlative laboratory studies to determine the relation of growth inhibition in tumor cell lines to the expression of the target antigens and clinical pharmacology of the agents, we observed that HD37 antibody was as effective in some respects as an antiproliferative agent as the IgG-HD37-SMPT-dgA immunotoxin. The antibody caused G1 arrest and hypophosphorylation of pRb. These results suggest that the negative growth regulatory effects of an antibody may complement the cytotoxic action of an immunotoxin in combined approaches.

A.持续输注联合治疗的初步I期研究 免疫毒素IgG-RFB 4-SMPT-dgA加IgG-HD 37-SMPT-dgA治疗难治性CD 19+， CD 22 + B细胞淋巴瘤。这项研究建立在以前的经验， 各自的免疫毒素用作单一试剂，并试图确定 同时服用鸡尾酒的安全性， 获得一些初步的疗效证据。两个剂量水平（5和10 mg/M2/192小时的每种毒素的研究。有初始 有证据表明，MTD将根据循环肿瘤是否 细胞是证据。3例无循环肿瘤的患者中有2例 细胞在较高剂量水平下出现III级毒性，而 3例循环肿瘤细胞患者均未发生III级 毒性或更大。初步证据表明，在同一 患者的免疫毒素处理不同，这取决于 靶抗原的表达。 B。免疫毒素和未结合抗体的相关性研究。在 相关的实验室研究，以确定生长的关系 抑制肿瘤细胞系中靶抗原的表达 和临床药理学的药物，我们观察到HD 37抗体， 在某些方面与抗增殖剂一样有效， IgG-HD 37-SMPT-dgA免疫毒素。抗体引起G1期阻滞， pRb的低磷酸化。这些结果表明，负增长 抗体的调节作用可以补充 联合方法中的免疫毒素。