Costimulatory chimeric antigen receptor T cells targeting IL13Rα2
Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes IL-13 or a variant thereof that binds interleukin-13Rα2 (IL13Rα2), a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.
1. A nucleic acid molecule comprising a nucleotide sequence encoding a chimeric antigen receptor molecule comprising the amino acid sequence of SEQ ID NO: 10.
2. An expression vector comprising the nucleic acid molecule of claim 1 .
3. The expression vector of claim 2 wherein the expression vector is a lentiviral vector.
4. The nucleic acid molecule of claim 1 further comprising a nucleotide sequence encoding a GMSCFRa signal sequence preceding the nucleotide sequence encoding the chimeric antigen receptor.
5. The nucleic acid molecule of claim 4 wherein the GMSCFRa signal sequence comprises the amino acid sequence of SEQ ID NO:2.
6. The nucleic acid molecule of claim 4 further comprising a nucleotide sequence encoding a T2A ribosome skip sequence following the nucleotide sequence encoding the chimeric antigen receptor.
7. The nucleic acid molecule of claim 6 wherein T2A ribosome skip sequence comprises the amino acid sequence of SEQ ID NO:8.
8. An expression vector comprising the nucleic acid molecule of claim 4 .
9. The expression vector of claim 8 wherein the expression vector is a lentiviral vector.
10. The nucleic acid molecule of claim 1 further comprising a nucleotide sequence encoding a T2A ribosome skip sequence following the nucleotide sequence encoding the chimeric antigen receptor.
11. The nucleic acid molecule of claim 10 wherein T2A ribosome skip sequence comprises the amino acid sequence of SEQ ID NO:8.
12. The nucleic acid molecule of claim 10 further comprising a nucleotide sequence encoding a truncated CD19 following the nucleotide sequence encoding the T2A ribosome skip sequence.
13. The nucleic acid molecule of claim 12 wherein the truncated CD19 comprises the amino acid sequence of SEQ ID NO:9.
14. The nucleic acid molecule of claim 12 wherein the truncated CD19 consists of the amino acid sequence of SEQ ID NO:9.
15. The nucleic acid molecule of claim 1 further comprising a nucleotide sequence encoding a truncated CD19.
16. The nucleic acid molecule of claim 15 wherein the truncated CD19 comprises the amino acid sequence of SEQ ID NO:9.