Artificial cell constructs for cellular manipulation
The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (T reg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound T reg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.
1. A method for treating an allograft rejection in a subject in need thereof, the method comprising administering to said subject at least one artificial particle comprising at least one soluble regulatory T cell stimulating factor or at least one chemotactic factor, whereby the method inhibits allograft rejection in the subject, wherein the at least one soluble regulatory T cell stimulating factor or the at least one chemotactic factor undergoes controlled release.
2. The method of claim 1 , wherein said artificial particle is porous.
3. The method of claim 1 , wherein said artificial particle comprises compartments.
4. The method of claim 3 , wherein said compartments comprise said at least one soluble regulatory T cell stimulating factor or said at least one chemotactic factor.
5. The method of claim 1 , wherein said controlled release is a short-term release.
6. The method of claim 5 , wherein said short-term release is between 30 minutes-24 hours.
7. The method of claim 1 , wherein said controlled release is a long-term release.
8. The method of claim 7 , wherein said long-term release is between 24 hours-1 year.
9. The method of claim 7 , wherein said long-term release is at least one year.
10. The method of claim 1 , wherein said at least one soluble regulatory T cell stimulating factor is CCL22.
11. The method of claim 1 , wherein said at least one soluble regulatory T cell stimulating factor is IL2.
12. The method of claim 1 , wherein said at least one soluble regulatory T cell stimulating factor TGFβ.
13. The method of claim 1 , wherein said at least one chemotactic factor is Vasoactive Intestinal Peptide.
14. The method of claim 1 , wherein said artificial particle is biodegradable.
15. The method of claim 1 , wherein said subject has received a skin allotransplant, corneal allotransplant, heart allotransplant, lung allotransplant, intestinal allotransplant, liver allotransplant, kidney allotransplant, pancreas allotransplant, islet cell allotransplant, bone allograft, limb allotransplant, or vascularized composite allotransplant.