The present invention relates to cell lines that produce ligands that bind
to human tumor 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 cell lines produce ligands that bind 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 tumor and
tumor regression activities of the TNF are enhanced; and the cytotoxicity
and receptor binding activities of the TNF are unaffected or enhanced on
tumor 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.