Technology evaluation: leukemia therapy, University of Pennsylvania

The University of Pennsylvania is developing an antisense oligonucleotide (AS ON) as a potential treatmentfor myelogenous leukemia. The 24-mer phosphorothioate (PS) ON targets the c-myb gene (codons 2 to 9), a regulator of transcription. In a pilot study, patient bone marrow was purged with the PS ON before being returned to the patient. In January 1997, it was reported that out of six evaluable patients, four demonstrated marked hematological remission with normalized white blood cell counts. A second phase I trial was initiated, in which myelogenous leukemia patients were treated with systemic infusions of the PS ON at doses of 0.3 to 2.0 mg/kg/dayfor 7 days. By January 1997, 18 patients had been treated, 12 showed stable disease and one patient in blast crisis experienced a transient reversal to the chronic phase of the disease. No dose-related toxicity was noted and c-myb mRNA and protein levels were halved. Preclinical studies in leukemic mice showed that the myb AS PS ON increased survival times 2- to 4-fold and reduced leukemic proliferation in the brain [229790]. The ON was originally developed and patented at Temple University and was being jointly developed by Lynx Therapeutics, however, this collaboration was terminated in 1996 [264351]. New phase I studies are starting in 1999, with INX-3001 (University of Pennsylvania c-myb AS PS) supported by the NIH and Inex Pharmaceuticals Corporation.