| 摘要 |
Disclosed are means of inducing antigen-specific tolerance through genetically modifying MSC to express antigens of interest in an inducible manner or constitutive manner. MSC have been demonstrated to suppress pathological immunity in an antigen-nonspecific manner in vitro and in vivo, including clinical trials of GVHD, Type 1 Diabetes, and Multiple Sclerosis. Administration of autoantigens in non-immunogenic routes, such as orally, intranasally, or delivered using immature dendritic cells has shown some signs of clinical efficacy, although effect has not been robust enough to allow for human therapeutic success. We disclose genetic modification of MSC to induce overexpression of autoantigens in a regulated manner in order to generate a universal donor antigen-specific tolerogenic vaccine as a treatment for autoimmunity. MSC are uniquely suited for this goal given their following properties: a) induction of T regulatory cells; b) suppression of T helper, T cytotoxic, and NK cells; c) downregulation of antigen presentation. |
