发明名称 |
Truncated epiderimal growth factor receptor (EGFRt) for transduced T cell selection |
摘要 |
A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways. Thus, EGFRt may be used as a non-immunogenic selection tool, tracking marker, a depletion tool or a suicide gene for genetically modified cells having therapeutic potential. |
申请公布号 |
US8802374(B2) |
申请公布日期 |
2014.08.12 |
申请号 |
US201213463247 |
申请日期 |
2012.05.03 |
申请人 |
City of Hope |
发明人 |
Jensen Michael C. |
分类号 |
C12Q1/68;C07K14/00 |
主分类号 |
C12Q1/68 |
代理机构 |
Perkins Coie LLP |
代理人 |
Perkins Coie LLP ;Sliger Lauren |
主权项 |
1. A genetically modified Epidermal Growth Factor Receptor (EGFR) gene, comprising a nucleotide sequence encoding a truncated non-immunogenic endogenous cell surface molecule, said cell surface molecule comprising an EGFR Domain III and an EGFR Domain IV; but lacking nucleotides all of the domains consisting of an EGFR Domain I, an EGFR Domain II, an EGFR Juxtamembrane Domain, and an EGFR Tyrosine Kinase Domain; wherein the truncated non-immunogenic endogenous cell surface molecule (i) does not have endogenous signaling or trafficking function; (ii) binds a therapeutic anti-EGFR antibody; (iii) does not bind an endogenous EGFR ligand; and (iv) acts as a marker. |
地址 |
Duarte CA US |