Allogeneic cell therapy: mirror effect

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/0783 (2010.01) A61K 35/14 (2006.01) A61K 39/00 (2006.01) A61P 37/02 (2006.01)

Patent

CA 2525596

A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the "Mirror Effect". In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the "mirror" of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The "mirror" of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti~tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non~ toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis~matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and/or radiation conditioning regimens.

L'invention concerne un procédé de manipulation de cellule allogénique en vue d'une utilisation dans des protocoles de traitement cellulaire allogénique. Ce procédé comprend une composition de lymphocytes T allogéniques hautement activée infusée dans des patients cancéreux immunocompétents afin d'éliciter un nouveau mécanisme immunitaire antitumoral appelé <= effet miroir >=. Contrairement aux protocoles thérapeutiques cellulaires allogéniques existants dans lesquels les lymphocytes T contenus dans la greffe à travers la greffe bénéfique versus tumeur (GVT) et la greffe nuisible versus effets hôtes (GVH), les cellules allogéniques de l'invention stimulent les lymphocytes T hôtes afin de transférer le <= miroir >= de ces effets. Le miroir à effet GVT consiste en un effet hôte versus tumeur (HVT). Le <= miroir >= de l'effet GVH consiste en un effet hôte versus greffe (HVG). L'efficacité et la généralisation de l'effet GVT antitumoral sont limitées par la toxicité aiguë de l'effet GVH. Dans cette invention, l'effet HVT antitumoral agit conjointement avec l'effet de rejet HVG non toxique. Les cellules allogéniques hautement activées de l'invention peuvent être utilisées en vue de stimuler l'immunité hôte dans une situation non concordante de HLA total chez des patients qui n'ont pas subis préalablement une transplantation de la moelle osseuse ou reçus des traitements chimiothérapeutiques et/ou des régimes de conditionnement par rayonnement.

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