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⢠No. . ⢠Circuit power supply components. IBM System/38 and System/38 ® Customer English The IBM System/38 instruction set consisted of .
Field of the Invention
The present invention relates generally to protein-based therapeutics. In particular, the invention relates to a hybrid polypeptide comprising a tumor necrosis factor (TNF) receptor fused to a cell surface molecule of the class I or II major histocompatibility complex, and hybrid polypeptides comprising multiple units of said hybrid polypeptides. The invention further relates to a method of producing hybrid polypeptides comprising a tumor necrosis factor receptor fusion protein and a cell surface molecule of the class I or II major histocompatibility complex, and hybrid polypeptides comprising multiple units of said hybrid polypeptides. The invention additionally relates to methods of using said hybrid polypeptides in the treatment or prevention of disease conditions, such as cancer.
2. Description of the Related Art
Tumor necrosis factor (TNF) is a proinflammatory cytokine that induces a variety of cellular responses, including cytotoxicity, induction of cellular adhesion molecules, induction of insulin-resistance and activation of nuclear transcription factors, including NFκB and AP1 (Ghosh, A., et al., Biochem. Biophys. Res. Commun. 216, 811-820 (1995); Ansmant, et al., J. Leukocyte Biol. 55, 806-812 (1994); Finck, et al., Science 233, 869-871 (1986); Beutler, et al., Nature 339, 623-625 (1989); Aggarwal, et al., Plasma Glucose, Lipids, and Blood Pressure: A Pathophysiological Approach, CRC Press, Boca Raton, Fla. (1990); Berk, J. Biol. Chem. 264, 5100-5108 (1989)). Because of its diverse role in the cellular response to infection, TNF has been implicated in the pathogenesis of a variety of disease conditions.
TNF-binding proteins have been described, including TNF-binding proteins isolated from rats (Lemsedun, et al., Eur. J. Biochem. 251:612-622 (1998); Gross, et al., Eur. J. Biochem
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