Surrogate tolerogenesis for the development of tolerance to...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/00 (2006.01) A01K 67/027 (2006.01) A61K 35/12 (2006.01) A61K 35/14 (2006.01) A61K 35/28 (2006.01) A61K 35/36 (2006.01) A61K 35/39 (2006.01) A61K 35/407 (2006.01) A61K 39/00 (2006.01) A61K 39/395 (2006.01)

Patent

CA 2163517

This invention provides a method for developing immune tolerance in xenogeneic organ graft recipients, in which lymphohematopoietic cells from an intended organ graft recipient are differentiated within a xenogeneic surrogate, such as a fetal animal. The figure illustrates one embodiment of the invention. After birth of the surrogate, the matured lympho-hematopoietic cells containing antigen specific regulatory cells, including suppressor cells, veto cells, select B cells, anti-idiotype antibodies, and other related factors responsible for antigen specific tolerance in a surrogate animal are reintroduced into the intended organ graft recipient, in conjunction with an organ transplant or a tissue transplant from the xenograft surrogate. The invention also provides an organ graft repopulated with cells from the intended organ graft recipient produced in a surrogate animal.

Ce procédé, qui permet de développer une tolérance immunitaire chez les sujets receveurs de greffons xénogènes, réalise, chez un substitut xénogène (par exemple, un foetus animal), la différentiation des cellules lympho-hématopoïétiques prélevées sur le receveur destinataire de la greffe d'organe. Voir la Figure (1) qui illustre l'un des modes de réalisation de l'invention. Après naissance du substitut, les cellules lympho-hématopoïétiques arrivées à maturité contiennent les cellules régulatrices spécifiques des antigènes, telles que les cellules suppressives, les cellules veto, les cellules de sélection B, les anticorps anti-idiotypes, ainsi que d'autres facteurs responsables de la tolérance spécifiques aux antigènes chez l'animal de substitution. Ces cellules lympho-hématopoïétiques sont réintroduites chez le sujet receveur conjointement avec le greffon (organe ou tissu) prélevé chez le substitut à xénogreffe. Avec cette invention, le greffon est recolonisé par les cellules du receveur destinataire produites par un animal de substitution.

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