IMMUNOTOXIN THERAPY OF HEMATOPOIETIC MALIGNANCIES

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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.