Acellular Pro-Tolerogenic Compositions for the Treatment/Prevention of Auto-Immune Diseases

摘要

This invention relates to pro-tolerogenic preparations capable of increasing the level of regulatory T cells (Treg) and/or decreasing the level of pro-inflammatory T cells (Th17) to induce anergy or immune tolerance. The pro-tolerogenic preparation is enriched in at least one species of miRNAs and is obtained by contacting two allogeneic leukocyte populations wherein at least one of the two populations is modified with a low-immunogenic biocompatible polymer. Therapeutic uses intended for the treatment/prevention of auto-immune diseases of such compositions are also provided.

主权项

1. A method of increasing a ratio of the level of regulatory T (Treg) cells to the level of pro-inflammatory T cells in a subject in need thereof, said method comprising administering to the subject a therapeutic amount of a pro-tolerogenic preparation obtained by a process comprising:
(i) associating a low-immunogenic biocompatible polymer to a cytoplasmic membrane of a first leukocyte to obtain a first modified leukocyte; (ii) contacting the first modified leukocyte with a second leukocyte under conditions to allow a pro-tolerogenic allo-recognition to provide a conditioned preparation, wherein the first leukocyte is allogeneic to the second leukocyte; (iii) removing the first modified leukocyte and the second leukocyte from the conditioned preparation under conditions to inhibit RNA degradation so as to obtain a composition enriched in acellular pro-tolerogenic components; and (iv) formulating the composition of step (iii), under conditions to inhibit RNA degradation, in the pro-tolerogenic preparation for administration to the subject;wherein the administration of the pro-tolerogenic preparation increases the ratio in the subject.