Cell
The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.
1. An engineered cell which comprises a CAR and a constitutively active Signal Transducer and Activator of Transcription (STAT) molecule,
wherein the constitutively active STAT molecule is
(a) a dimerized and constitutively active STAT molecule comprising a first STAT polypeptide having a first dimerization domain and a second STAT polypeptide having a second dimerization domain which second dimerization domain specifically binds the first dimerization domain and wherein the dimerization of the first and second STAT polypeptides structurally changes the STAT molecule to a constitutively active form,
(b) a constitutively active STAT molecule comprising a first STAT polypeptide linked to a second STAT polypeptide by a linker sequence, or
(c) a constitutively active STAT molecule comprising a Gain of Function (GOF) mutation.
2. A cell according to claim 1 (b).
3. A cell according to claim 1 (a).
4. A nucleotide construct comprising a first nucleotide sequence encoding a CAR and a second nucleotide sequence encoding a constitutively active STAT molecule,
wherein the constitutively active STAT molecule is
(a) a dimerized and constitutively active STAT molecule comprising a first STAT polypeptide having a first dimerization domain and a second STAT polypeptide having a second dimerization domain which second dimerization domain specifically binds the first dimerization domain and wherein the dimerization of the first and second STAT polypeptides structurally changes the STAT molecule to a constitutively active form,
(b) a constitutively active STAT molecule comprising a first STAT polypeptide linked to a second STAT polypeptide by a linker sequence, or
(c) a constitutively active STAT molecule comprising a Gain of Function (GOF) mutation.
5. A pharmaceutical composition comprising a plurality of cells according to claim 1 .
6. A method for making a cell according to claim 1 , which comprises the step of introducing into a cell a nucleic acid sequence encoding the constitutively active or inducible STAT molecule.
7. A cell according to claim 1 (c).