Chimeric T cell
The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) and a signal transduction modifying protein, selected from one of the following: (i) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM), but lacks a kinase domain; (ii) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM) but lacks a phosphatase domain; (iii) a fusion protein which comprises (a) an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) or from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM); and (ii) a heterologous domain.
1. An isolated T cell, which comprises a chimeric antigen receptor (CAR), wherein the T cell further comprises a SHP-2 domain lacking a SHP-2 phosphatase domain, and wherein the sequence of the SHP-2 domain is SEQ ID NO: 11 or SEQ ID NO: 12.
2. A nucleic acid construct, which comprises: a first nucleic acid sequence encoding a chimeric antigen receptor (CAR); and a second nucleic acid sequence encoding a SHP-2 domain lacking a SHP-2 phosphatase domain, wherein the sequence of the SHP-2 domain is SEQ ID NO: 11 or SEQ ID NO; 12.
3. A vector, which comprises the nucleic acid construct according to claim 2 .
4. The vector according to claim 3 , which is a retroviral or lentiviral vector.
5. A pharmaceutical composition comprising a plurality of the isolated T cells according to claim 1 .