IMMUNOTOXIN THERAPY OF HEMATOPOIETIC MALIGNANCIES

淋巴瘤和白血病含有分化抗原， 在免疫系统外或干细胞上发现， 用于靶向癌症治疗的有用靶点。 其中之一就是IL-2 我们已经在临床试验中有了抗Tac（Fv）PE 38。 R. Kreitman先前已经表明，IL 6-PE 664 glu对 从多发性骨髓瘤患者分离的骨髓瘤细胞。 R. Kreitman已经制备了一批临床用的IL 6-PE 664 glu， 阿肯色州大学的一项骨髓净化研究。 我们 等待本研究主药物文件的批准， 启动。 R. Kreitman还设计了一种循环排列的形式 IL 4-PE 38 KDEL对星形细胞瘤有很强的细胞毒性。 我们 他的合作者Raj Puri（FDA）已经证明星形细胞瘤具有IL 4， 而大脑中的其他细胞则没有。 FDA已经给出了 美国允许提交IND，在患有以下疾病的患者中检测cpIL 4-PE 38 KDEL 不能手术的星形细胞瘤 这项研究将在约翰 韦恩癌症中心的罗伯特兰德博士生产后， 代理的临床批次。 E.曼斯菲尔德和D.菲茨杰拉德有 产生了二硫键连接的免疫毒素（RFB 4（dsFv）PE 38），其针对 CD 22，一种存在于许多淋巴瘤上的抗原。 RFB 4（dsFv）PE 38非常 对表达抗原的细胞系具有细胞毒性，导致 小鼠肿瘤，猴子耐受性很好。 临床批次 将在MARP制备RFB 4（dsFv）PE 38，I期研究将 携带 在国家癌症研究所的临床科学部工作

Lymphomas and leukemias contain differentiation antigens which are not found outside the immune system or on stem cells and therefore are useful targets for targeted cancer therapy. One of these is the IL-2 receptor and we already have anti-Tac(Fv)PE38 in clinical trials. R. Kreitman has previously shown that IL6-PE664glu is cytotoxic to myeloma cells isolated from patients with multiple myeloma. R. Kreitman has prepared a clinical batch of IL6-PE664glu to be used in a bone marrow purging study at the University of Arkansas. We are awaiting approval of the master drug file for this study to be initiated. R. Kreitman has also designed a circularly permuted form of IL4-PE38KDEL which is very cytotoxic to astrocytomas. Our collaborator, Raj Puri (FDA), has shown that astrocytomas have IL4 receptors whereas other cells in the brain do not. The FDA has given us permission to file an IND to test cpIL4-PE38KDEL in patients with inoperable astrocytomas. The study will be carried out at the John Wayne Cancer Center by Dr. Robert Rand following production of a clinical batch of the agent. E. Mansfield and D. FitzGerald have produced a disulfide linked immunotoxin (RFB4(dsFv)PE38) directed at CD22, an antigen present on many lymphomas. RFB4(dsFv)PE38 is very cytotoxic to cell lines expressing the antigen, causes regression of tumors in mice, and is very well tolerated by monkeys. A clinical lot of RFB4(dsFv)PE38 will be prepared at the MARP and a Phase I study will be carried out in the Division of Clinical Sciences at NCI.