Methods of treating skin conditions using inhibitors of the CD2/LFA-3 interaction
View Patent ↗Methods of using inhibitors of the CD2/LFA-3 interaction in treating skin conditions characterized by increased T cell activation and abnormal antigen presentation in the dermis and epidermis in mammals, including humans. Such conditions include psoriasis, UV damage, e.g., photoaging, atopic dermatitis, cutaneous T cell lymphoma such as mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
1. A method of preventing or treating skin conditions characterized by increased T cell activation and abnormal antigen presentation in the dermis and epidermis, comprising the step of administering to a mammal a first agent that binds to LFA-3 or CD2 selected from the group consisting of an LFA-3 polypeptide, a CD2 polypeptide, an anti-CD2 antibody homolog, and an anti-LFA-3 antibody homolog, in combination with a therapeutic or prophylactic second agent, wherein the second agent is selected from the group consisting of: cyclosporin A, prednisone, FK506, methotrexate, steroids, retinoids, and nitrogen mustard.
2. The method of claim 1 , wherein the first agent is a soluble LFA-3 polypeptide or an immunoglobulin (Ig) fusion thereof.
3. The method of claim 1 , wherein the first agent comprises a soluble LFA-3 polypeptide fused to all or part of an immunoglobulin heavy chain hinge region and all or part of a heavy chain constant region.
4. The method of claim 1 , wherein the first agent comprises a fusion protein comprising the amino terminal 92 amino acids of mature LFA-3, the C-terminal 10 amino acids of a human IgG1 hinge region and the CH2 and CH3 regions of a human IgG1 heavy chain constant domain.
5. The method of claim 1 , wherein the first agent is LFA3TIP (amino acids 1-319 of SEQ ID NO:8).
6. The method of claim 1 , wherein the first agent is encoded by an insert contained in plasmid pSAB152, deposited with American Type Culture Collection under the accession number ATCC 68720.
7. The method of claim 1 , wherein the condition is psoriasis.
8. The method of claim 2 , wherein the condition is psoriasis.
9. The method of claim 3 , wherein the condition is psoriasis.
10. The method of claim 4 , wherein the condition is psoriasis.
11. The method of claim 5 , wherein the condition is psoriasis.
12. The method of claim 6 , wherein the condition is psoriasis.
13. The method of claim 1 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyodenna gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
14. The method of claim 2 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
15. The method of claim 3 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
16. The method of claim 4 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyodenna gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
17. The method of claim 5 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
18. The method of claim 6 , wherein the condition is elected from the group consisting of atopic dermatitis, cutaneous T cell lymphoma, mycosis fungoides, allergic and irritant contact dermatitis, lichen planus, alopecia areata, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, and urticaria.
19. The method according to claim 1 , wherein the first and second agent are administered concurrently.
20. The method according to claim 2 , wherein the first and second agent are administered concurrently.
21. The method according to claim 3 , wherein the first and second agent are administered concurrently.
22. The method according to claim 4 , wherein the first and second agent are administered concurrently.
23. The method according to claim 5 , wherein the first and second agent are administered concurrently.
24. The method according to claim 6 , wherein the first and second agent are administered concurrently.
25. The method according to claim 1 , wherein the first and second agent are administered sequentially.
26. The method according to claim 2 , wherein the first and second agent are administered sequentially.
27. The method according to claim 3 , wherein the first and second agent are administered sequentially.
28. The method according to claim 4 , wherein the first and second agent are administered sequentially.
29. The method according to claim 5 , wherein the first and second agent are administered sequentially.
30. The method according to claim 6 , wherein the first and second agent are administered sequentially.
31. The method of claim 1 , wherein the mammal is a human.
32. The method of claim 2 , wherein the mammal is a human.
33. The method of claim 4 , wherein the mammal is a human.
34. The method of claim 5 , wherein the mammal is a human.
35. The method of claim 1 , wherein the first agent is administered at a dose between about 0.001 and about 50 mg agent per kg body weight.
36. The method of claim 2 , wherein the first agent is administered at a dose between about 0.001 and about 50 mg agent per kg body weight.
37. The method of claim 4 , wherein the first agent is administered at a dose between about 0.001 and about 50 mg agent per kg body weight.
38. The method of claim 5 , wherein the first agent is administered at a dose between about 0.001 and about 50 mg agent per kg body weight.
39. The method of claim 1 , wherein the first agent is administered at a dose between about 0.01 and about 10 mg agent per kg body weight.
40. The method of claim 2 , wherein the first agent is administered at a dose between about 0.01 and about 10 mg agent per kg body weight.
41. The method of claim 4 , wherein the first agent is administered at a dose between about 0.01 and about 10 mg agent per kg body weight.
42. The method of claim 5 , wherein the first agent is administered at a dose between about 0.01 and about 10 mg agent per kg body weight.
43. The method of claim 1 , wherein the first agent is administered at a dose between about 0.1 and about 4 mg per kg body weight.
44. The method of claim 2 , wherein the first agent is administered at a dose between about 0.1 and about 4 mg per kg body weight.
45. The method of claim 4 , wherein the first agent is administered at a dose between about 0.1 and about 4 mg per kg body weight.
46. The method of claim 5 , wherein the first agent is administered at a dose between about 0.1 and about 4 mg per kg body weight.
47. The method of claim 1 , wherein the first agent is administered intramuscularly, intravenously or subcutaneously.
48. The method of claim 2 , wherein the first agent is administered intramuscularly, intravenously or subcutaneously.
49. The method of claim 4 , wherein the first agent is administered intramuscularly, intravenously or subcutaneously.
50. The method of claim 5 , wherein the first agent is administered intramuscularly, intravenously or subcutaneously.
51. The method according to claim 1 , wherein the first agent is an anti-CD2 or anti-LFA-3 antibody homolog.
52. The method of claim 51 , wherein the antibody homolog is a humanized or chimeric antibody homolog.
53. The method of claim 51 , wherein the first agent is a monoclonal anti-LFA-3 antibody produced by a hybridoma selected from the group consisting of hybridomas having Accession Nos. ATCC HB 10693 (1E6), ATCC HB 10694 (HC-1B11), ATCC HB 10695 (7A6), and ATCC HB 10696 (8B8).
54. The method of claim 51 , wherein the first agent is selected from the group consisting of an Fab fragment, an Fab′ fragment, an F(ab′) 2 fragment, an F(v) fragment and an intact immunoglobulin heavy chain of an anti-LFA-3 antibody homolog.
55. The method of claim 51 , wherein the first agent is selected from the group consisting of an Fab fragment, an Fab′ fragment, an F(ab′) 2 fragment, an F(v) fragment and an intact immunoglobulin heavy chain of an anti-CD2 antibody homolog.
56. The method of claim 1 , wherein the first agent is a soluble CD2 polypeptide.
57. The method of claim 1 , wherein the second agent is cyclosporine A.
58. The method of claim 2 , wherein the second agent is cyclosporine A.
59. The method of claim 4 , wherein the second agent is cyclosporine A.
60. The method of claim 5 , wherein the second agent is cyclosporine A.
61. The method of claim 51 , wherein the second agent is cyclosporine A.
62. The method of claim 56 , wherein the second agent is cyclosporine A.
63. The method of claim 1 , wherein the second agent is methotrexate.
64. The method of claim 2 , wherein the second agent is methotrexate.
65. The method of claim 4 , wherein the second agent is methotrexate.
66. The method of claim 5 , wherein the second agent is methotrexate.
67. The method of claim 51 , wherein the second agent is methotrexate.
68. The method of claim 56 , wherein the second agent is methotrexate.