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산업원천기술개발사업 성과발표회 : 좌장: 김승욱 교수(고려대학교)

Development of Fc fusion protein for autoimmune disease using IL-23 antagonist

초록

영어

A p40-hyFc is a Fc fusion protein consisting of human p40 (a member of IL-12 family) and hybrid Fc (hyFc) derived from human IgD and IgG4 Fc regions. The p40 has been well known as a natural antagonist of IL-12 and IL-23 (1). Recently, it was reported that Th17 cell is a main regulator for autoimmune diseases and expanded by IL-23 (2), suggesting that the blockage of IL-23 signaling by long-acting p40 protein could be new approach to treat autoimmune diseases. The human p40-hyFc was demonstrated to specifically block IL-23 signaling in PBMCs from rheumatoid arthritis patients and mouse p40-hyFc (derivative of human p40-hyFc) also inhibited IL-23-mediated signaling in vitro and could decrease arthritis index score in mice collagen-induced arthritis (CIA) model In PK analysis using three cynomolgus monkeys, single subcutaneous injection with human p40-hyFc showed long half-life in monkeys. There was no significant increase in CBC and lymphocytes and no detectable Ab responses against human p40-hyFc. In cross-reactivity test, the human p40-hyFc did not show cross-reactivity with rodent, but did with monkeys. Therefore, the rhesus monkey model of CIA is the only available option to evaluate the efficacy of IL-12p40-hyFc in vivo. At present, the efficacy of human p40-hyFc was being evaluated in monkey CIA model in Nertherland primate center. To perform preclinical study, a stable cell line expressing human p40-hyFc was established, then MCB/WCB manufacturing and their characterizations are being conducted in Apptec company in USA. The process development for cultivation, purification, and analysis for p40-hyFc has been
performed during this study. Since there are non-responders to commercially available drugs such as Enbrel (TNFR-Fc) and Orencia (CTLA-4-Fc) targeting to soluble TNF- and CTLA4, respectively, human p40-hyFc could be a novel drug with different action mechanism and be used in combination with these therapeutics for patients.

저자정보

  • Sehwan Yang Research Institute of Genexine
  • Jeongsook Lee Research Institute of Genexine
  • Mi-Ra Cho Catholic Research Institute of Medical Science
  • Kyungho Lee Kolon Life Science
  • Yongjoon Jeong Kolon Life Science
  • Jeongsoon Park Progen
  • Sanghoon Ahn Progen
  • Younjoo Kyung Progen
  • Sunghee Lee Progen

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