Truncated epiderimal growth factor receptor (EGFRt) for transduced T cell selection
US8802374B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | May 3, 2012 |
| Grant date | Aug 12, 2014 |
| Priority date | — |
| Expiry date | May 3, 2032 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12Y207/10001
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.