Rimiducid (AP1903; i.v.,0.01, 0.1, 1, 10, and 100 mg/kg) elicits a dose-dependent decrease in serum human GH levels, with a half-maximal effective dose of 0.4±0.1 mg/kg.
The human fibrosarcoma line HT1080 is engineered to express stably a fusion protein comprising a myristoylation sequence, two copies of F36V-FKBP, and the human first apoptosis signal (Fas) intracellular domain. Rimiducid (AP1903) elicits potent and dose-dependent apoptotic death of these engineered cells in culture, with an EC 50 of ≈0.1 nM. Maximal killing occurred in the presence of 3 to 10 nM Rimiducid (AP1903), and the IC 50 is approximately 0.2 nM. LV′VFas-transduced T lymphocytes expressing high levels of CD25 (top panel) are eliminated by with 66%±7.5% (n=10) efficiency. When cells are examined after CD25 expression returned to basal levels, 63%±4.7% (n=9) killing is observed after Rimiducid treatment.
Musechem
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