Tumour necrosis factor binding ligands

Abstract

Abstract of the Disclosure The present invention relates to ligands which bind to human tumour necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. In preferred forms the ligand binds to TNF in a manner such that the induction of endothelial procoagulant activity of the TNF is inhibited; the binding of TNF to receptors on endothelial cells is inhibited; the induction of fibrin deposition in the tumour and tumour regression activities of the TNF are enhanced; and-the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumour cells. The ligand is preferably an antibody, F(ab) fragment, single domain antibody (dABs) single chain antibody or a serum binding protein. It is preferred, however, that the ligand is a monoclonal antibody or F(ab) fragment thereof.

Description

Detailed Description of the Invention[0001]This application is a continuation of application Serial No. 09 / 736,630, now U.S. Pat. No. 6,593,457, filed December13, 2000, which is a continuation of application Serial No. 09 / 364,039 (now U.S. Patent No. 6,416,757), filed July 30, 1999, which is a continuation of application Serial No. 08 / 823,893, filed March 17, 1997 (now U.S. Patent No. 5,959,087), which is a continuation of application Serial No. 08 / 344,133, filed November 23, 1994 (now U.S. Patent No. 5,644,034), which is a continuation-in-part of application Serial No. 07 / 828,956, filed February 18, 1992 (now abandoned), which is a national phase filing of PCT / AU90 / 00337, filed August 7, 1990, which claims the benefit of Australian applications AU PJ5662, filed August 7, 1989, and AU PJ7576, filed November 24, 1989, the disclosures of which are incorporated herein by reference in their entirety.[0002]The present invention relates to ligands which bind to human tumour necrosis facto...

AI Technical Summary

Benefits of technology

These monoclonal antibodies and ligands effectively inhibit or enhance TNF activities as needed, reducing side effects and improving therapeutic outcomes by selectively targeting TNF's biological functions, thereby enhancing tumor regression while minimizing coagulation activation.

Problems solved by technology

While TNF infusion into cancer patients in stage 1 clinical trials has resulted in tumour regression, side-effects such as thrombocytopaenia, lymphocytopaenia, hepatotoxicity, renal impairment and hypertension have also been reported.

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