Methods and compositions for modulating lymphangiogenesis, e.g., to treat transplant rejection, in a subject
View Patent ↗Methods of modulating the occurrence of lymphangiogenesis in a subject are provided. In some instances, the method is a method of treating transplant rejection in the subject. Aspects of the methods include administering to the subject an effective amount of: a first antagonist for a tyrosine kinase receptor and a second antagonist for an integrin receptor. In some embodiments, the methods include enhancing survival of transplanted tissue in a subject. Aspects of the invention further include compositions, e.g., pharmaceutical compositions and kits that find use in methods of the invention.
1. A method of reducing the occurrence of lymphangiogenesis in a corneal transplant subject having inflamed and vascularized high risk of rejection, the method comprising:
administering to the subject an amount of:
a first antagonist for VEGFR-3, wherein the first antagonist is a neutralizing antibody or binding fragment thereof that specifically binds to VEGFR-3; and
a second antagonist for VLA-1, wherein the second antagonist is a neutralizing antibody or binding fragment thereof that specifically binds to VLA-1;
effective to reduce the occurrence of lymphangionesesis in a corneal transplant in the subject having a high risk of rejection.
2. The method according to claim 1 , wherein the first and second antagonists are neutralizing antibodies.
3. The method according to claim 1 , wherein the corneal transplant subject has an inflamed and vascularized cornea.
4. The method according to claim 1 , further comprising transplanting corneal tissue in the subject.
5. The method according to claim 1 , further comprising transplanting tissue in a graft bed of the subject.
6. The method according to claim 5 , wherein the administering is performed prior to the transplanting.
7. The method according to claim 5 , wherein the administering is performed during the transplanting.
8. The method according to claim 5 , wherein the administering is performed after the transplanting.
9. The method according to claim 5 , wherein the graft bed of the subject is inflamed and vascularized.
10. The method according to claim 9 , wherein the method comprises reducing inflammatory lymphangiogenesis in the graft bed.
11. The method according to claim 1 , wherein the first and second antagonists are administered simultaneously.
12. The method according to claim 1 , wherein the first and second antagonists are administered sequentially.
13. The method according to claim 5 , wherein the method comprises reducing inflammatory lymphangiogenesis at a grafting border between the transplanted tissue and the graft bed.
14. The method according to claim 5 , wherein the method comprises reducing the occurrence of opacity of the corneal tissue.
15. The method according to claim 5 , wherein the method does not significantly inhibit blood vessel growth in the tissue.
16. The method according to claim 15 , wherein the method comprises inhibiting lymphatic vessel growth into the transplanted tissue.
17. The method according to claim 4 , wherein the method comprises enhancing survival of the transplanted organ in the subject.
18. The method according to claim 5 , wherein the method comprises enhancing survival of the transplanted tissue in the subject.
19. The method according to claim 18 , wherein the method comprises reducing inflammatory lymphangiogenesis of the corneal tissue.
20. The method according to claim 18 , wherein the method comprises reducing the occurrence of opacity of the corneal tissue.
21. The method according to claim 19 , wherein the method does not significantly inhibit blood vessel function in the tissue.
22. The method according to claim 18 , wherein the method comprises inhibiting lymphatic vessel function in the tissue.