Selective cell-death-inducing binary enzyme system

A drug for use in the treatment and/or prophylaxis of cancer or tumor diseases containing an inactive form of granzyme B comprising the sequence set forth in SEQ ID NO:

• 2 or a nucleic acid encoding it, or a functional variant of either, and tobacco etch virus protease comprising the sequence set forth in SEQ ID NO:
• 4 or SEQ ID NO:
• 5 or a nucleic acid encoding the tobacco etch virus protease or a functional variant of either, wherein the tobacco etch virus protease releases an active form of granzyme B comprising the sequence set forth in SEQ ID NO:
• 2.

A drug containing

• an inactive form of granzyme B, wherein the inactive form of granzyme B is a fusion protein comprising the sequence set forth in SEQ ID NO:
• 2 or a nucleic acid encoding it, or a functional variant of either, wherein ENLYFQ (SEQ ID NO:
• 6) or ENLYFQG (SEQ ID NO:
• 7) is ligated with the N-terminus of SEQ ID NO:
• 2 and SEQ ID NO:
• 2 or a functional variant thereof is obtained or released by means of cleavage by tobacco etch virus protease at ENLYFQ (SEQ ID NO:
• 6) or ENLYFQG (SEQ ID NO:
• 7), and
• tobacco etch virus protease or a nucleic acid encoding the tobacco etch virus protease or a functional variant of either.

A process for introducing a drug or combination preparation comprising

• i) introducing an inactive form of granzyme B comprising a nucleic acid encoding a polypeptide having the sequence set forth in SEQ ID NO:
• 2, or a functional variant thereof, and a nucleic acid encoding tobacco etch virus protease or a functional variant thereof, together or separately from one another, in at least one vehicle,
• ii.) introducing the vehicle into a tumor cell, wherein the inactive form of granzyme B is expressed in the tumor cell, and
• iii.) producing an active form of granzyme B in the tumor cell and inducing cell death in the tumor cell.