TARGETING THE INNATE IMMUNE SYSTEM TO INDUCE LONG-TERM TOLERANCE AND TO RESOLVE MACROPHAGE ACCUMULATION IN ATHEROSCLEROSIS
Methods and compositions for inducing long-term tolerance by hybrid nanoparticles are provided. Compositions and formulations comprising hybrid nanoparticles with inherent affinity for innate immune cells are provided.
1 . A method of inducing immune tolerance comprising administering to a patient an effective amount of (i) a composition comprising a high-density lipoprotein-derived nanoparticle (HDL) which comprises an mTOR inhibitor.
2 . The method of claim 1 , wherein the mTOR inhibitor is rapamycin or a pharmaceutically acceptable salt, solvate, poly-morph, tautomer or prodrug thereof.
3 - 4 . (canceled)
5 . The method of claim 1 , wherein the patient is susceptible to or has an atherosclerotic condition including: coronary atherosclerosis, diabetic atherosclerosis, a sequela of atherosclerosis, such as acute coronary syndrome, myocardial infarction, angina pectoris, peripheral vascular disease, intermittent claudication, myocardial ischemia, stroke, heart failure and combinations thereof.
6 - 25 . (canceled)
26 . A composition comprising a high-density lipoprotein-derived nanoparticle (HDL) which comprises an m-TOR inhibitor.
27 - 28 . (canceled)
29 . The composition of claim 26 , wherein the mTOR inhibitor is rapamycin or a pharmaceutically acceptable salt, solvate, polymorph, tautomer or prodrug thereof, formulated as rapamycin nanoparticle (mTOR-HDL or rapamycin-HDL).
30 . A pharmaceutical composition comprising a) a pharmaceutically effective amount of the composition of claim 26 and b) a pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant.
31 - 43 . (canceled)
44 . A method for prolonging allograft survival in a patient, comprising administering an effective amount of the pharmaceutical composition of claim 26 to a patient in need thereof.
45 . A method for decreasing dendritic cell stimulatory capacity in a patient, comprising administering an effective amount of the composition of claim 26 to a patient in need thereof.
46 . A method for promoting the development of regulatory macrophages in a patient, comprising administering an effective amount of the composition of claim 26 to a patient in need thereof.
47 . A method of inducing transplant tolerance in a patient comprising administering an effective amount of the composition of claim 26 to a patient in need thereof.
48 . A method of targeting myeloid cells in a patient comprising administering an effective amount of the composition of claim 26 to a patient in need thereof, wherein the mTOR-HDL reduces Mo/MΦ numbers in the circulation of the patient.
49 . The method of claim 44 , wherein the composition specifically targets myeloid cells.
50 . The method of claim 44 , wherein the patient has undergone a transplant and 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, bone marrow, or vascular tissue.
51 . The method of claim 50 , wherein the transplanted tissue is an intact organ.
52 . The method of claim 44 wherein the patient has received an allogeneic tissue or organ transplant.
53 . The method of claim 44 , wherein the method is performed prior to performance of an allogeneic tissue or organ transplant.
54 . The method of claim 44 , wherein the method is performed in conjunction, with an allogeneic tissue or organ transplant.
55 . The method of claim 44 wherein the method is performed within at least, two weeks after an allogeneic tissue or organ transplant.
56 . The method of claim 44 , wherein the subject is human.
57 . The method of claim 44 , wherein the composition is administered intravenously or intra-arterially.
58 - 59 . (canceled)