Methods for detecting, identifying, isolating, and...

C - Chemistry – Metallurgy – 12 – N

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C12N 5/0783 (2010.01) A61K 35/14 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) G01N 33/554 (2006.01) G01N 33/569 (2006.01) A61K 38/00 (2006.01) C07K 14/705 (2006.01) C07K 16/28 (2006.01)

Patent

CA 2227334

The lymphocyte activation gene (LAG-3) is a member of the immunoglobulin superfamily that is selectively transcribed in human activated T and NK cells. Surface LAG-3 expression correlated with IFN-.gamma. but not IL-4, production in antigen-stimulated T-cells and it was up-regulated by IL-12 and is preferentially associated with CD4+ T-cells producing Th1-type cytokines. The presence of LAG-3 on the surface of Th1 lymphocytes is used as a marker to detect and identify Th1 lymphocytes and differentiate them from Th2 lymphocytes. Monoclonal antibodies to LAG-3 are used in methods of detecting and isolating Th1 cells as well as methods of diagnosing Th1-mediated disease. The present invention also relates to methods of treating infectious diseases, cancer, and disorders associated with Th1/Th2 imbalance.

Le gène d'activation des lymphocytes (LAG-3), qui est un membre de la superfamille des immunoglobulines, est transcrit sélectivement dans les lymphocytes T et les cellules tueuses naturelles activées de l'homme. Il y a une corrélation entre l'expression de la protéine de surface LAG-3 et la production d'IFN-.gamma. dans les lymphocytes T stimulés par un antigène, mais pas celle d'IL-4, et cette production est stimulée par IL-12. Cette production est associée, de préférence, avec les lymphocytes T CD4+ produisant des cytokines du type Th-1. La présence de LAG-3 sur la surface des lymphocytes Th1 est utilisée comme marqueur pour détecter et identifier les lymphocytes Th1 et les distinguer des lymphocytes Th2. On utilise des anticorps monoclonaux dirigés contre LAG-3 pour détecter et isoler les cellules Th1, ainsi que pour diagnostiquer des maladies associées à Th1. La présente invention concerne également des procédés de traitement de maladies infectieuses, du cancer et de troubles associés à un déséquilibre Th1/Th2.

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