This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoshio-Hoshino, N. Articles by Nishimoto, N. Search for Related Content PubMed PubMed Citation Articles by Yoshio-Hoshino, N. Articles by Nishimoto, N.

Establishment of a New Interleukin-6 (IL-6) Receptor Inhibitor Applicable to the Gene Therapy for IL-6–Dependent Tumor

¹ Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan and ² Division of Human Gene Therapy, Department of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, Alabama

Requests for reprints: Norihiro Nishimoto, Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, 1-3, Yamadaoka, Suita City, Osaka Prefecture 565-0871, Japan. Phone: 81-6-6879-4436; Fax: 81-6-6879-4437; E-mail: norihiro{at}fbs.osaka-u.ac.jp.

Interleukin-6 (IL-6) is a key molecule involved in the pathogenesis of several inflammatory diseases and malignancies. Treatments that inhibit IL-6 mitigate the clinical conditions of such diseases. Here, we report on the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody which specifically blocks IL-6 signaling. This NRI consists of VH and VL of tocilizumab in a single-chain fragment format dimerized by fusing to the Fc portion of human immunoglobulin G₁. The binding activity to IL-6 receptor and the biological activity of the purified NRI were found to be similar to those of parental tocilizumab. Because NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. We administered an adenovirus vector encoding NRI to mouse i.p. and monitored the serum NRI level and growth reduction property on S6B45, an IL-6–dependent multiple myeloma cell line, in vivo. Adequate amount of the serum NRI level to exert anti-IL-6 action could be obtained by the NRI gene introduction combined with adenovirus gene delivery, and this treatment inhibited the in vivo S6B45 cell growth significantly. These findings indicate that NRI is a promising agent applicable to the therapeutic gene delivery approach for IL-6–driven diseases. [Cancer Res 2007;67(3):871–5]

This article has been cited by other articles:

				T. Ara, L. Song, H. Shimada, N. Keshelava, H. V. Russell, L. S. Metelitsa, S. G. Groshen, R. C. Seeger, and Y. A. DeClerck Interleukin-6 in the Bone Marrow Microenvironment Promotes the Growth and Survival of Neuroblastoma Cells Cancer Res., January 1, 2009; 69(1): 329 - 337. [Abstract] [Full Text] [PDF]

				Y.-T. Tai, M. Dillon, W. Song, M. Leiba, X.-F. Li, P. Burger, A. I. Lee, K. Podar, T. Hideshima, A. G. Rice, et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu Blood, August 15, 2008; 112(4): 1329 - 1337. [Abstract] [Full Text] [PDF]

				J. A. Katzel, P. Hari, and D. H. Vesole Multiple Myeloma: Charging Toward a Bright Future CA Cancer J Clin, September 1, 2007; 57(5): 301 - 318. [Abstract] [Full Text] [PDF]