Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo

作者: Henning Walczak , Robert E. Miller , Kiley Ariail , Brian Gliniak , Thomas S. Griffith

DOI: 10.1038/5517

关键词:

摘要: To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms human (hu) and murine (mu) TRAIL to promote stabilize formation trimers. Both were biologically active, inducing apoptosis both target cells in vitro with similar specific activities. In contrast fulminant hepatotoxicity LZ-huCD95L vivo, administration either LZ-huTRAIL or LZ-muTRAIL did not seem toxic normal tissues mice. Finally, repeated treatments actively suppressed growth TRAIL-sensitive mammary adenocarcinoma cell line MDA-231 CB.17 (SCID) mice, histologic examination tumors from SCID mice treated demonstrated clear areas apoptotic within 9-12 hours injection.

参考文章(47)
P R Galle, W J Hofmann, H Walczak, H Schaller, G Otto, W Stremmel, P H Krammer, L Runkel, Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. Journal of Experimental Medicine. ,vol. 182, pp. 1223- 1230 ,(1995) , 10.1084/JEM.182.5.1223
Larry W. Moreland, Scott W. Baumgartner, Michael H. Schiff, Elizabeth A. Tindall, Roy M. Fleischmann, Arthur L. Weaver, Robert E. Ettlinger, Stanley Cohen, William J. Koopman, Kendall Mohler, Michael B. Widmer, Consuelo M. Blosch, Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. The New England Journal of Medicine. ,vol. 337, pp. 141- 147 ,(1997) , 10.1056/NEJM199707173370301
J Cohen, Cytokines as mediators of graft-versus-host disease. Bone Marrow Transplantation. ,vol. 3, pp. 193- 197 ,(1988)
Peter Vandenabeele, Wim Declercq, Johan Grooten, Walter Fiers, Bart Vanhaesebroeck, Both TNF receptors are required for TNF-mediated induction of apoptosis in PC60 cells. Journal of Immunology. ,vol. 154, pp. 2904- 2913 ,(1995)
Michel Revel, Amichai Schattner, Interferons: cytokines in autoimmunity. Ciba Foundation Symposium 129 - Autoimmunity and Autoimmune Disease. ,vol. 129, pp. 223- 233 ,(2007) , 10.1002/9780470513484.CH15
Takehiro Yatomi, Shigekazu Nagata, Takashi Suda, Masato Tanaka, Masato Tanaka, Norio Nakamura, Lethal effect of recombinant human Fas ligand in mice pretreated with Propionibacterium acnes. Journal of Immunology. ,vol. 158, pp. 2303- 2309 ,(1997)
Anthony Ceramil, Bruce Beutler, The role of cachectin/TNF in endotoxic shock and cachexia Immunology Today. ,vol. 9, pp. 28- 31 ,(1988) , 10.1016/0167-5699(88)91353-9
Richard J. Armitage, Tumor necrosis factor receptor superfamily members and their ligands Current Opinion in Immunology. ,vol. 6, pp. 407- 413 ,(1994) , 10.1016/0952-7915(94)90119-8
Pascal Schneider, Nils Holler, Jean-Luc Bodmer, Michael Hahne, Karl Frei, Adriano Fontana, Jürg Tschopp, Conversion of Membrane-bound Fas(CD95) Ligand to Its Soluble Form Is Associated with Downregulation of Its Proapoptotic Activity and Loss of Liver Toxicity Journal of Experimental Medicine. ,vol. 187, pp. 1205- 1213 ,(1998) , 10.1084/JEM.187.8.1205
T. S. Griffith, T. Brunner, S. M. Fletcher, D. R. Green, T. A. Ferguson, Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege Science. ,vol. 270, pp. 1189- 1192 ,(1995) , 10.1126/SCIENCE.270.5239.1189