Method for producing T cells compatible with allogeneic transplantation

摘要

The present invention relates to engineered T cells, methods for their preparation, and their use as pharmaceuticals, particularly for immunotherapy. The engineered T cells of the present invention, for example, selectively select a gene encoding β2-microglobulin (B2M) and / or a gene encoding a class II major histocompatibility complex transactivator (CIITA) by DNA cleavage. B2M and / or CIITA expression is inhibited by using rare-cutting endonucleases that can be inactivated or by using nucleic acid molecules that inhibit B2M and / or CIITA expression And At least one gene encoding a component of the T cell receptor selectively inactivates, for example, the gene encoding the TCR component by DNA cleavage so that the T cell is further non-alloreactive It can be inactivated by using a rare-cutting endonuclease. Furthermore, immunosuppressive polypeptides can be expressed on these modified T cells in order to prolong the survival of these modified T cells in the host organism. Such modified T cells are particularly suitable for allogeneic transplantation, particularly because both the risk of rejection by the host immune system and the risk of developing graft-versus-host disease are both low. The present invention paves the way for standard and affordable adoptive immunotherapy strategies using T cells to treat cancer, infectious diseases, and autoimmune diseases.