METHOD FOR GENERATING T-CELLS COMPATIBLE FOR ALLOGENIC TRANSPLANTATION

摘要

The present invention relates to engineered T-cells, methods of making them, and their use as medicines, especially for immunotherapy. The engineered T-cells of the present invention can selectively inactivate a gene encoding B2M and/or CIITA, for example, by using nucleic acid molecules that inhibit the expression of B2M and/or CIITA by DNA cleavage. Inhibition of expression of beta 2-microglobulin (B2M) and/or class II major histocompatibility complex transactivator (CIITA) by using rare-cleaving endonucleases It is characterized. In order to further make T-cells non-alloreactive, for example, rare-cutting endonucleases capable of selectively inactivating the gene encoding the TCR element by DNA cleavage. By use, at least one gene encoding an element of the T-cell receptor is inactivated. In addition, expression of immunosuppressive polypeptides can be performed on those modified T-cells to prolong the survival of these modified T cells in a host organism. Such modified T-cells are particularly suitable for allogeneic transplants, in particular because they reduce both the risk of development of the graft versus host disease and the risk of rejection of the host's immune system. The present invention opens the way to standard and suitable adoptive immunotherapy using T-cells to treat cancer, infections and autoimmune diseases.