Methods of using interleukin-2 mutants with reduced toxicity
Interleukin-2 (IL-2) mutants having reduced toxicity, which include full-length IL-2, truncated forms of IL-2 and forms of IL-2 that are linked to another molecule are disclosed herein. Particular substitutions within IL-2, particularly within the permeability enhancing peptide region of IL-2 achieve substantial reduction of vasopermeability activity as compared to a wildtype form of the mutant IL-2 while retaining many of the immune activating properties of IL-2. Invention IL-2 mutants can be used to stimulate the immune system of an animal and may be used in the treatment of various disorders and conditions.
1. A method of decreasing solid tumor size in a cancer patient having a cancer that is responsive to interleukin-2 therapy, said method comprising administering an effective amount of an interleukin-2 (IL-2) mutant with reduced vasopermeability activity compared to a wildtype form of the IL-2 mutant, said mutant being His55Tyr, wherein said wildtype form of the human IL-2 mutant is human IL-2 having the sequence corresponding to SEQ ID NO. 3.
2. The method of claim 1 , wherein said IL-2 mutant is linked to an antibody.
3. The method of claim 2 , wherein said antibody is a tumor targeting antibody.
4. The method of claim 3 , wherein said tumor targeting antibody is chTNT-3.
5. The method of claim 1 , wherein said IL-2 mutant further comprises a mutation outside the permeability enhancing peptide region of IL-2.
6. The method of claim 5 , wherein said mutant further comprises a mutation at one or more of positions 1-21 or 59-133 of IL-2.
7. The method of claim 6 , wherein said IL-2 mutant further comprises a mutation in a lysine at position 88.
8. The method of claim 1 , wherein said cancer patient has renal cell carcinoma.
9. The method of claim 1 , wherein said cancer patient has melanoma.
10. The method of claim 1 , wherein said IL-2 mutant is administered in combination with a therapeutic agent.
11. The method of claim 1 , wherein said IL-2 mutant is administered as a component of a vaccine.
12. The method of claim 1 , wherein said IL-2 mutant comprises a full-length IL-2 molecule.