title: A four-week repeated study of intravenous toxicity of recombinant human interleukin-2 in Sprague-Dawley rats.
abstract: 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 9×10(6), 18×10(6), and 36×10(6)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 9×10(6)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.
authors.affiliation: Department of Pathology, Biotoxtech Co. Ltd., 686-2 Yangcheong-ri, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.
authors.forename: Mi Ju
authors.initials: MJ
authors.lastname: Lee
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Myoung Jun
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.forename: Kyeoung-Nam
authors.initials: KN
authors.lastname: Ko
authors.forename: Duyeol
authors.initials: D
authors.lastname: Kim
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho-Song
authors.initials: HS
authors.lastname: Jang
authors.forename: Yeongjun
authors.initials: Y
authors.lastname: Baik
authors.forename: Sunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kang
authors.forename: Jong-Koo
authors.initials: JK
authors.lastname: Kang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D013810:Therapeutic Equivalency; D059551:Toxicity Tests, Subacute
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins