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Yeda R&D Co. Ltd
Abstract ID: 1487
The ability to redirect at will the specificity of regulatory T cells (Treg) towards any target of interest, enables their clinical application as an effective immunosuppressors of a...
The ability to redirect at will the specificity of regulatory T cells (Treg) towards any target of interest, enables their clinical application as an effective immunosuppressors of a wide range of inflammatory disorders including autoimmune diseases, graft rejection, graft versus host syndromes and inflammation induced malignancies. The current treatments of a large fraction of these disorders is symptomatic, non-specific and of a short range while the application of antigen specific Treg offers disease-specific and durable therapy.
Accordingly, the market place is large and of a great need for such a therapy.
The level of Treg in the human body is very low and although some suppressive effect of normal Treg could be shown in animal models, it is rather impractical to obtain an effective therapeutic dose of such cells for patients treatment. In contrary, redirected Treg prepared as taught by the current invention have demonstrated more than 10 fold suppressive, therapeutic effect after adoptive transfer into mice suffering from acute colitis. In practice, in one embodiment, of the invention, CD4+CD25+ Treg could be isolated from the patient's PBL, activated, transduced with retrovectors harbouring chimeric receptors genes composed of scFv of antibody specific to a target antigen of the inflamed organ. Alternatively, Treg could be induced by the ectopic expression of FoxP3 in normal T cells and transduced as above. Such redirected Treg could be further expended and selected in vitro and then systemically introduced into the patient. The target antigen, can, but not necessarily be the pathogen. It should be recognized by the infused Treg and activate them at the inflamed site to execute their suppressive activity.
The technology beyond this invention relies on ex-vivo modification of the patient's own Treg, using DNA encoding chimeric receptor whose recognition unit is engineered to bind the desired antigen. The resulting cells are selected and propagated in-vitro and can be then administered to the patient as well to be stored frozen for further treatments.
Suppression of autoimmune diseases such as colitis, multiple sclerosis, rheumatoid arthritis, diabetes type I, etc. Please enquire quoting reference no. 1487 regarding licensing or codevelopment partnerships.
Last Updated May 2015