A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague–Dawley rats

Interleukin-2 (IL-2) is a lymphokine with a potential role in cancer therapy. Many clinical trials of recombinant human IL-2 (rhIL-2) have been conducted to treat malignant renal carcinoma, melanoma, leukemia, lymphoma, multiple myeloma. BMI Korea has developed a method to manufacture rhIL-2 in bulk using Escherichia coli as a biosimilar. Prior to conducting human clinical trials, 4-week repeated toxicity study of rhIL-2 was conducted. In this study, rhIL-2 was administered intravenously to rats at doses of 9 × 106, 18 × 106, and 36 × 106 IU/kg/day over a period of 4 weeks. Adverse effects were observed in RBC, HGB, HCT, reticulocyte, mesenteric lymph node from middle dose, and changes of total bilirubin, femoral bone marrow, thymus, and clinical signs were observed at high dose. Local irritation was determined at low dose of female rats and at middle dose of male ones. Taken together, no observed adverse effect levels (NOAEL) was determined at dose of 9 × 106 IU/kg/day in male, and NOAEL was determined under the dose level in female rats. It suggests that present rhIL-2 is less toxic prior produced rhIL-2 and may be contribute more effective cancer-treatment strategy in human.