The present invention relates to methods for developing engineered T cells for immunotherapy that are non alloreactive. The present invention relates to methods for modifying T cells by inactivating both genes encoding T cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases in particular TALE nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides to precisely target a selection of key genes in T cells which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.
