CD154 blockade therapy for pancreatic islet tissue transplantation
Methods and compositions for inhibiting rejection of insulin-producing tissue in a graft recipient, as well as methods and compositions for prolonging graft survival or function; for reversing graft rejection or restoring function of an impaired graft; and, for inducing immunological tolerance to grafted, insulin-producing tissue. The present methods and compositions are suitable for treatment or prophylaxis of defects in metabolic control of blood glucose homeostasis, including defects manifested as diabetes mellitus (DM).
1 . A method of inhibiting or reversing rejection or prolonging survival of an insulin-producing tissue graft by a human graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interrupter to the human graft recipient, wherein the CD40:CD154 binding interruptor is an antibody or antibody derivative having the antigen-specific binding characteristics of the 5c8 antibody produced by ATCC Accession No. HB 10916.
2 . (canceled)
3 . (canceled)
4 . A method of preserving function of grafted insulin-producing tissue or restoring function of impaired, grafted insulin-producing tissue in a human graft recipient, comprising the step of administering an effective amount of a CD40:CD154 binding interrupter to the human graft recipient wherein the CD40:CD154 binding interrupter is an antibody or antibody derivative having the antigen-specific binding characteristics of the 5c8 antibody produced by ATCC Accession No. HB 10916.
5 . (canceled)
6 . (canceled)
7 . (canceled)
8 . (canceled)
9 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is whole pancreatic tissue or isolated pancreatic islets.
10 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is a cell population comprising isolated adult islet B cells, isolated fetal islet d cells, cultured islet B cells, or immortalized islet B cells.
11 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is a cell population comprising host cells stably or inducibly expressing an insulin gene.
12 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is physically separated from tissues of the recipient by an immunoisolation device.
13 . (canceled)
14 . (canceled)
15 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is allogeneic to the graft recipient.
16 . The method according to claim 1 or claim 4 , wherein the insulin-producing tissue is xenogeneic to the graft recipient.
17 . (canceled)
18 . The method according to claim 1 or claim 4 , wherein the human graft recipient is afflicted with an impairment of metabolic control of glucose metabolism.
19 . The method according to claim 1 or claim 4 , wherein the human graft recipient is afflicted with diabetes mellitus.
20 . A method of restoring metabolic control of glucose metabolism in a human in need thereof, comprising the steps of:
a) implanting an effective amount of insulin-producing tissue in the human; and,
b) administering an effective amount of a CD40:CD154 binding interrupter to the human, wherein the CD40:CD154 binding interrupter is an antibody or antibody derivative having the antigen-specific binding characteristics of the 5c8 antibody produced by ATCC Accession No. HB 10916.
21 . (canceled)
22 . The method according to claim 20 , wherein the antibody or antibody derivative is administered prior to tissue implantation.
23 . The method according to claim 22 , comprising the additional step of repeating administration of the antibody or antibody derivative at least twice within a two-week period following tissue implantation.
24 . The method according to claim 23 , comprising the further additional step of repeating administration of the antibody or antibody derivative at least one month after tissue implantation.
25 . The method according to claim 24 , comprising the still further additional step of repeating administration of the antibody or antibody derivative on a monthly basis, beginning at least two months after tissue implantation.
26 .- 39 . (canceled)