Methods of preventing rejection of transplanted tissue by administering anti-CD40L antibody and HLA-E-bearing composition
A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.
1. A method for preventing rejection of a tissue transplanted from a donor subject into a recipient subject comprising:
a) administering to the recipient subject, prior to transplantation of the tissue, (i) a plurality of peripheral blood mononuclear cells (PBMCs) from the donor subject, wherein the PBMCs have been irradiated and do not proliferate in vivo, and (ii) an anti-CD40 ligand (anti-CD40L) antibody; and
b) administering to the recipient subject, subsequent to transplantation of the tissue, (i) an HLA-E/IgG fusion protein, (ii) an HLA-E/type B peptide tetramer, (iii) a dendritic cell-derived, HLA-E-bearing exosome loaded with type B self peptides, or (iv) a membrane-bound, HLA-E-bearing composition comprising at least one type B peptide,
wherein the type B self peptide comprises the amino acid sequence set forth in SEQ ID NO: 1.
2. The method of claim 1 , further comprising administering to the recipient subject an immunosuppressant pharmaceutical during step a), during step b), or during both step a) and step b).
3. The method of claim 1 , wherein the type B self peptide is Hsp60sp peptide comprising the amino acid sequence set forth in SEQ ID NO: 2 or in SEQ ID NO: 3.
4. The method of claim 1 , wherein the administration of step b) is intravenous, subcutaneous, intramuscular or oral.
5. The method of claim 1 , wherein the anti-CD40L antibody is administered to the recipient subject for a period of up to 10 weeks.
6. The method of claim 1 , wherein the plurality of PBMCs from the donor subject is administered to the recipient subject optionally in two separate portions, a first portion 2 to 3 weeks before transplantation, and then optionally a second portion which is administered to the recipient subject about seven days after the first portion is administered.
7. The method of claim 2 , wherein the immunosuppressant pharmaceutical is cyclosporine A, FK506 or rapamycin.
8. The method of claim 2 , wherein an immunosuppressant pharmaceutical is administered daily for up to 10 weeks after administration of the plurality of PBMCs, or first portion thereof.
9. The method of claim 1 , wherein the tissue is transplanted into the recipient subject two to three weeks after administration of the plurality of PBMCs or first portion thereof.
10. The method of claim 1 , further comprising administering an anti-thromboembolic agent to the recipient subject during the period of administration of the anti-CD40L antibody.
11. The method of claim 1 , wherein the transplanted tissue is lung tissue, heart tissue, kidney tissue, liver tissue, retinal tissue, corneal tissue, skin tissue, pancreatic tissue, intestinal tissue, genital tissue, ovary tissue, bone tissue, tendon tissue, or vascular tissue.
12. The method of claim 1 , wherein the transplanted tissue is an intact organ.