| 专利名称 | COMBINED T CELL RECEPTOR GENE THERAPY OF CANCER AGAINST MHC I AND MHC II-RESTRICTED EPITOPES OF THE TUMOR ANTIGEN NY-ESO-1 | ||
| 申请号 | EP16712262 | 申请日 | |
| 公开(公告)号 | EP3268385B1 | 公开(公告)日 | |
| 申请(专利权)人 | Max Delbr點k Centrum f黵 Molekulare Medizin in der Helmholtz Gemeinschaft | 发明人 | BLANKENSTEIN Thomas; PONCETTE Lucia; CHEN Xiaojing |
| 专利来源 | 国家知识产权局 | 转化方式 | |
| 摘要 |
The present invention relates to the field of immunotherapy, in particular adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one T cell receptor alpha chain construct and/or TCR beta chain construct of a TCR construct capable of specifically binding to an epitope from NY-ESO-1 (also designated CTAG-1) in complex with a human MHC, wherein the TCR alpha chain construct and/or the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having at least 90% sequence identity to an amino acid selected from SEQ ID NO : 1-20. The invention provides TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC I, and, for the first time, TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC II molecules, and thus enables a combined adoptive T cell therapy with both recombinant CD4+ and recombinant CD8+ T cells. The invention also provides proteins and host cells corresponding to said TCR constructs, as well as the medical use of such constructs, in particular, in the diagnosis, prevention and/or treatment of a proliferative or viral disease, wherein, preferably, both TCR constructs restricted to MHC I and MHC II molecules are provided in a kit. The invention also relates to a mouse transgenic for the human TCR loci and human HLA-DR4, ABabDR4 mouse. |
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