The present invention provides for a modified TIE-2 ligand which has been
altered by addition, deletion or substitution of one or more amino acids,
or by way of tagging, with for example, the Fc portion of human IgG-1, but
which retains its ability to bind the TIE-2 receptor. The invention
further provides for a modified TIE-2 ligand which is a chimeric TIE-2
ligand comprising at least a portion of a first TIE-2 ligand and a portion
of a second TIE-2 ligand which is different from the first. In a specific
embodiment, the invention further provides for a chimeric TIE ligand
comprising at least a portion of TIE-2 Ligand-1 and a portion of TIE-2
Ligand-2. In addition the present invention provides for isolated nucleic
acid molecule encoding the modified TIE-2 ligands described. The invention
also provides for therapeutic compositions as well as a method of blocking
blood vessel growth, a method of promoting neovascularization, a method of
promoting the growth or differentiation of a cell expressing the TIE
receptor, a method of blocking the growth or differentiation of a cell
expressing the TIE receptor and a method of attenuating or preventing
tumor growth in a human.