Patent EA-002550-B1 (EA)
Title: Cd154 blockade therapy for pancreatic islet tissue transplantation
Inventor: KENYON NORMA S
IPC: A61P3/08
Filed: 1998-06-19
Abstract: 1. A method of inhibiting rejection of an insulin-producing tissue graft by a graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interruptor to the graft recipient, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 2. A method of prolonging survival of grafted insulin-producing tissue in a graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interruptor to the graft recipient, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 3. A method of reversing rejection of grafted insulin-producing tissue in a graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interruptor to the graft recipient, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 4. A method of preserving function of grafted insulin-producing tissue in a graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interruptor to the graft recipient, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 5. A method of restoring function of impaired, grafted insulin-producing tissue in a graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interruptor to the graft recipient, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 6. A method according to claims 1 to 5, wherein said blocking agent is a monoclonal antibody. 7. A method according to claim 6, wherein the monoclonal antibody has the antigen specific binding characteristics of the 5c8 antibody produced by ATCC Accession No. HB 10916. 8. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is whole pancreatic tissue or isolated pancreatic islets. 9. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is a cell population comprising isolated adult islet β cells, isolated fetal islet β cells, cultured islet β cells, or immortalized islet β cells. 10. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is a cell population comprising host cells stably or inducibly expressing an insulin gene. 11. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is physically separated from tissues of the recipient by an immunoisolation device. 12. A method according to claim 11, wherein the immunoisolation device comprises a semipermeable barrier defining an isolation chamber in which the insulin producing tissue is disposed. 13. A method according to claim 12, wherein the immunoisolation device is a capsule or a microcapsule. 14. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is allogeneic to the graft recipient. 15. A method according to claim 1, 2, 3, 4 or 5, wherein the insulin-producing tissue is xenogeneic to the graft recipient. 16. A method according to claim 1, 2, 3, 4 or 5, wherein the graft recipient is human. 17. A method according to claim 17 wherein the graft recipient is afflicted with an impairment of metabolic control of glucose metabolism. 18. A method according to claim 18 wherein the graft recipient is afflicted with diabetes mellitus. 19. A method of restoring metabolic control of glucose metabolism in a mammal in need thereof, comprising the steps of: a) implanting an effective amount of insulin-producing tissue in the mammal; and, b) administering an effective amount of a CD40:CD154 binding interruptor to the mammal, wherein said CD40:CD154 binding interruptor is a blocking agent specifically bound with CD154, its antigen-binding fragment or a derivative thereof. 20. A method according to claim 19, wherein the CD40:CD154 binding interruptor is a monoclonal antibody having the antigen-specific binding characteristics of the 5c8 antibody produced by ATCC Accession No. HB 10916. 21. A method according to claim 20, wherein the monoclonal antibody is administered prior to tissue implantation. 22. A method according to claim 21, comprising the additional step of repeating administration of the monoclonal antibody at least twice within a two-week period following tissue implantation. 23. A method according to claim 22, comprising the further additional step of repeating administration of the monoclonal antibody at least one month after tissue implantation. 24. A method according to claim 23, comprising the still further additional step of repeating administration of the monoclonal antibody on a monthly basis, beginning at least two months after tissue implantation. 25. A method according to claim 19, comprising the additional step of: c) implanting an effective amount of a tolerizing agent into the mammal. 26. A method according to claim 25, wherein the tolerizing agent is bone marrow tissue that is MHC-compatible with the insulin-producing tissue. 27. A method according to claim 25, wherein the tolerizing agent is bone marrow tissue that is syngeneic with the insulin-producing tissue. 28. A method according to claim 26 or 27, wherein the bone marrow tissue is whole bone marrow. 29. A method according to claim 26 or 27, wherein the bone marrow tissue is a population of CD34(+) hematopoeitic cells. 30. A method according to claim 29 wherein the CD34(+) hematopoeitic cells are CD40(-).