Antigen-specific induction of peripheral immune tolerance

Details Antigen-specific induction of peripheral immune tolerance Antigen-specific induction of peripheral immune tolerance

A - Human Necessities

61

K

A61K 39/00 (2006.01) A61K 39/35 (2006.01) A61K 48/00 (2006.01) A61P 37/08 (2006.01)

Patent

CA 2368225

Fas ligand (CD95L) induces apoptosis in activated T cells through the process of Activation Induced Cell Death (AICD). Gelatin nanoparticles are virus sized gelatin-protein-DNA complexes which can encapsulate multiple DNA vectors and proteins, and which are thought to act by increasing in vivo transfection of antigen presenting cells. By injecting mice with gelatin nanoparticles containing a murine Fas ligand (CD95L) DNA vector and a .beta.-galactosidase (LacZ) model antigen vector, the T cell response specific for .beta.-gal was ablated without effecting the response to a secondary antigen. In effect, this "tolerization" injection induceS antigen specific peripheral tolerance in study mice, and is applicable to the treatment of autoimmune diseases when self-antigens such as Myelin Basic Protein are co-delivered with the Fas ligand.

L'invention concerne un ligand Fas (CD95L) induisant l'apoptose dans des lymphocytes T activés, par un processus de mort cellulaire programmée (AICD). Les nanoparticules de gélatine sont des complexes de gélatine, protéine et ADN dimensionnées pour les virus, pouvant contenir des vecteurs d'ADN et des protéines multiples, et conçus pour accroître la transfection in vivo de cellules présentant l'antigène. En injectant des nanoparticules de gélatine contenant un vecteur d'ADN de ligand Fas (CD95L) murine à des souris et un vecteur d'antigène expérimental .beta.-galactosidase (LacZ), ou supprime la réponse du lymphocyte T spécifique pour .beta.-gal sans que cela ait un effet sur la réponse à un antigène secondaire. En effet, cette injection <= tolérée >= induit une tolérance périphérique des antigènes spécifiques dans les souris à l'étude. Ladite injection est applicable au traitement de maladies auto-immunes, lorsque des autoantigènes, tels que la protéine basique myélinique, sont co-administrés avec le ligand Fas.

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