MONOCLONAL ANTIBODY TREATMENT OF AIDS-RELATED LYMPHOMA

艾滋病相关淋巴瘤的单克隆抗体治疗

• 批准号: 3200017
• 负责人: DAVID J STRAUS
• 金额: $ 15.28万
• 依托单位: MEMORIAL HOSPITAL FOR CANCER & ALLIED DI
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-16 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3200017
• 关键词: AIDS; AIDS /HIV diagnosis; AIDS therapy; B lymphocyte; HIV infections; Hodgkin's disease; Retroviridae; T lymphocyte; antiviral antibody; bone marrow disorder; cell mediated cytotoxicity; clinical trials; combination cancer therapy; cytogenetics; dosage; human immunodeficiency virus; human subject; human therapy evaluation; immunoglobulin G; immunosuppressive; immunosuppressive antileukocyte serum; immunotoxicity; lymphoma; monoclonal antibody; neoplasm /cancer immunotherapy; neoplasm /cancer radionuclide therapy

AIDS-associated lymphoma has a poor prognosis. Although in a subpopulation of patients the lymphoma appears to be arrested with chemotherapy, in others infections in the setting of increased immunosuppression and myelosuppression may be fatal. Clearly less toxic alternative treatment approaches are needed. Monoclonal antibody (mAb) therapy is one such approach. Antitumor activity with minimal toxicity has been demonstrated here with 131-I-labeled OKB7, an IgG2b reactive with CD21, the EBV receptor, in B cell lymphomas not associated with AIDS. Peripheral blood B cells counts are depressed while T cells levels are maintained with OKB7 treatment. This may limit further T cell suppression in AIDS patients. Twenty to 25 patients will be treated with OKB7 labeled with 200 mCi of 13I-I in 4 divided doses. mAb R24 is an IgG3, reactive with the cell membrane ganglioside GD-3, which fixes human complement and mediates cytotoxicity. Tumor responses have been documented here against malignant melanoma, and studies are in progress with patients with Hodgkin's disease, T cell lymphoma and thymoma. Twelve to 20 patients with Hodgkin's disease and HIV infection will be treated with escalating doses of R24. JD118 is a complement-fixing IgM with highly restricted reactivity with normal and malignant B cells. It will be potentially active in unconjugated form in. B cell lymphoma. Like R24 it is unlikely to be myelosuppressive or toxic to T cells. Twelve to 20 patients with AIDS-associated B cell lymphomas will be treated with escalating doses of antibody. Ancillary laboratory studies will also be performed. Quantitative studies of retroviral load and production are necessary parameters of toxicity and may indicate the most effective way of combining mAb and antiretroviral therapy in the future. Serum and cellular markers will permit monitoring of AIDS activity. Serial cytogenetic studies and molecular biological studies, in particular of the breakpoints for MYC in these patients,may give further insights into the biology of AIDS-related B cell lymphomas.

艾滋病相关淋巴瘤预后差。 虽然在一个 淋巴瘤患者亚群似乎被逮捕， 化疗，在其他感染的情况下， 免疫抑制和骨髓抑制可能致命。 毒性明显较低 需要替代治疗方法。 Monoclonal antibody（mAb） 治疗就是这样一种方法。 抗肿瘤活性和最小毒性 131-I标记的OKB7，一种IgG 2b反应性抗体， 与CD21，EBV受体，在B细胞淋巴瘤中不相关， 艾滋病 外周血B细胞计数降低，而T细胞水平 用OKB7治疗。 这可能会进一步限制T细胞 抑制艾滋病患者。 20至25名患者将接受以下治疗： 用200 mCi的13 I-I标记OKB 7，分4次给药。mAb R24是一种 IgG 3，与细胞膜神经节苷脂GD-3反应，其固定人 补体并介导细胞毒性。 肿瘤反应已经 这里记录了对恶性黑色素瘤的治疗， 何杰金氏病、T细胞淋巴瘤和胸腺瘤患者。 12至20名霍奇金病和艾滋病毒感染者将在 用递增剂量的R24治疗 JD118是一种补体结合IgM， 与正常和恶性B细胞的反应性高度受限。 它 将以非缀合形式具有潜在活性。B细胞淋巴瘤。 与R24一样，它不太可能对T细胞具有骨髓抑制或毒性。 12至20名艾滋病相关B细胞淋巴瘤患者将接受 用递增剂量的抗体治疗 辅助实验室研究 也将被执行。 逆转录病毒载量的定量研究， 生产是毒性的必要参数，可能表明最 为今后单克隆抗体与抗逆转录病毒治疗的有效结合提供了新的途径。 血清和细胞标记物将允许监测艾滋病活动。 系列细胞遗传学研究和分子生物学研究， 特别是这些患者中MYC的断点，可能会进一步 艾滋病相关B细胞淋巴瘤的生物学见解。