Recombinant proteins containing Shiga-like toxin and vascular endothelial growth factor fragments

An isolated polypeptide comprising:

• (1) the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof, wherein said subunit has the nucleic acid sequence of SEQ ID NO:9 or a truncated or mutated version thereof;
• and
• (2) human vascular endothelial growth factor, or a truncated or mutated version thereof, wherein said growth factor has the nucleic acid sequence of SEQ ID NO:10, or a truncated or mutated version thereof;
• wherein said isolated polypeptide possesses ribosome inactivating activity.

An expression vector, comprising:

• (1) a nucleic acid encoding a fusion protein comprising the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof;
• and human vascular endothelial growth factor, or a truncated or mutated version thereof;
• and
• (2) a promoter sequence operably linked to said nucleic acid to allow expression of said nucleic acid;
• said expression vector comprising the nucleic acid sequence of SEQ ID NO:11.

A method of inactivating ribosomes in a cell, comprising the steps of:

• (a) contacting a cell with a polypeptide comprising:
• (1) the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof, said subunit having the nucleic acid sequence of SEQ ID NO:9, or a truncated or mutated version thereof;
• and
• (2) human vascular endothelial growth factor, or a truncated or mutated version thereof, said growth factor having the nucleic acid sequence of SEQ ID NO:10, or a truncated or mutated version thereof;
• under conditions which permit said polypeptide to be internalized into said cell and inactivate ribosomes in said cell.

A composition for inhibiting endothelial cell growth in a patient, comprising:

• (A) a fusion protein comprising the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof;
• and human vascular endothelial growth factor, or a truncated or mutated version thereof, said fusion protein possessing ribosome inactivating activity;
• and
• (B) a pharmaceutically acceptable carrier;
• wherein said A subunit of said Shiga-like bacterial toxin, or a truncated or mutated version thereof, is encoded by the nucleic acid sequence of SEQ ID NO:9, and wherein said human vascular endothelial growth factor, or a truncated or mutated version thereof, is encoded by the nucleic acid sequence of SEQ ID NO:11.

A method of treating a patient suffering from a pathophysiological condition that depends on angiogenesis, comprising:

• providing to said patient an effective amount of a composition comprising a fusion protein comprising the A subunit of Shiga-like bacterial toxin, or a truncated or mutated version thereof;
• and human vascular endothelial growth factor, or a truncated or mutated version thereof, said fusion protein possessing ribosome inactivating activity;
• and a pharmaceutically acceptable carrier;
• wherein said A subunit of said Shiga-like bacterial toxin, or a truncated or mutated version thereof, is encoded by the nucleic acid sequence of SEQ ID NO:9, and wherein said human vascular endothelial growth factor, or a truncated or mutated version thereof, is encoded by the nucleic acid sequence of SEQ ID NO:11.