Chemotherapeutic methods and compositions
Disclosed herein are methods and compositions for enhancing the cell-killing activity of anti-neoplastic agents by inhibiting the activity of a lysyl oxidase-type enzyme. Also disclosed are methods for screening for chemotherapeutic agents, and for molecules that enhance the activity of chemotherapeutic agents, using cells grown on an extracellular matrix.
1. A method for enhancing the cell killing activity of an anti-neoplastic agent, the method comprising:
contacting a cell that is resistant to the anti-neoplastic agent with the anti-neoplastic agent and an inhibitor of LOXL2, wherein the anti-neoplastic agent is a nucleic acid;
wherein the cell is growing in the presence of an extracellular matrix containing collagen and the inhibitor is an antibody that specifically binds to LOXL2,
whereby the cell killing activity of the anti-neoplastic agent is enhanced.
2. The method of claim 1 , wherein the cell is in culture.
3. The method of claim 1 , wherein the cell is present in a tumor.
4. The method of claim 1 , wherein the nucleic acid is a siRNA.
5. The method of claim 1 , wherein the collagen comprises type I collagen.
6. A method for killing a malignant cell, the method comprising:
contacting the malignant cell with an anti-neoplastic agent and an inhibitor of LOXL2, wherein the anti-neoplastic agent is a nucleic acid;
wherein the malignant cell is growing in the presence of an extracellular matrix containing collagen and the inhibitor is an antibody that specifically binds to LOXL2,
whereby the malignant cell is killed.
7. The method of claim 6 , wherein the malignant cell is in culture.
8. The method of claim 6 , wherein the malignant cell is present in a tumor.
9. The method of claim 6 , wherein the nucleic acid is a siRNA.
10. The method of claim 6 , wherein the collagen comprises type I collagen.
11. A method for reversing resistance of a malignant cell to an anti-neoplastic agent, the method comprising:
contacting the malignant cell, which is resistant to the anti-neoplastic agent, with the anti-neoplastic agent and an inhibitor of LOXL2, wherein the anti-neoplastic agent is a nucleic acid,
wherein the malignant cell is growing in the presence of an extracellular matrix containing collagen and the inhibitor is an antibody that specifically binds to LOXL2,
whereby the resistance of the malignant cell to the anti-neoplastic agent is reversed.
12. The method of claim 11 , wherein the malignant cell is in culture.
13. The method of claim 11 , wherein the malignant cell is present in a tumor.
14. The method of claim 11 , wherein the nucleic acid is a siRNA.
15. The method of claim 11 , wherein the collagen comprises type I collagen.
16. The method of claim 1 , wherein the antibody is monoclonal.
17. The method of claim 1 , wherein the antibody is an antibody fragment.
18. The method of claim 17 , wherein the antibody fragment is selected from the group consisting of scFv, Fab, and Fab 2 fragments.
19. The method of claim 1 , wherein the antibody is human or humanized.
20. The method of claim 6 , wherein the antibody is monoclonal.
21. The method of claim 6 , wherein the antibody is an antibody fragment.
22. The method of claim 21 , wherein the antibody fragment is selected from the group consisting of scFv, Fab, and Fab 2 fragments.
23. The method of claim 6 , wherein the antibody is human or humanized.
24. The method of claim 11 , wherein the antibody is monoclonal.
25. The method of claim 11 , wherein the antibody is an antibody fragment.
26. The method of claim 25 , wherein the antibody fragment is selected from the group consisting of scFv, Fab, and Fab 2 fragments.
27. The method of claim 11 , wherein the antibody is human or humanized.