METHODS FOR MODIFYING RESISTANT ALLOGENIC AND IMMUNOSUPPRESSANT T-LYMPHOCYTES FOR IMMUNOTHERAPY

The present invention provides methods for developing immunotherapy-modified T cells that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T cells by inactivating target genes encoding an immunosuppressive agent and a T cell receptor， in particular genes encoding CD52 and TCR. This method implements the use of specific rare cleavage endonucleases， in particular TALE nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides， to precisely target a selection of key genes in T lymphocytes， which are available from donors or from a culture of primary cells. The invention paves the way for adopting standard and accessible immunotherapy strategies for treating cancer and viral infections.