JPWO2020163634A5 - - Google Patents

Claims (21)

A polynucleotide encoding a chimeric cytokine receptor polypeptide,
a first nucleic acid encoding IL-7;
a second nucleic acid encoding a tethered strand;
a third nucleic acid encoding an extracellular domain of an IL-7 receptor to which said IL-7 is linked via said tethering strand;
a fourth nucleic acid encoding a transmembrane domain; and
A fifth nucleic acid encoding the intracellular domain of IL-21 receptor
including
A polynucleotide wherein the transmembrane domain links the extracellular domain of the IL-7 receptor to the intracellular domain of the IL-21 receptor. Polynucleotide according to claim 1 , wherein the length of the tethered strand is 3 to 30 amino acids long. 2. The polynucleotide of claim 1, wherein said transmembrane domain comprises the transmembrane domain of an IL-7 receptor. 2. The polynucleotide of claim 1, wherein the first nucleic acid comprises a nucleotide sequence having at least 95% sequence identity with SEQ ID NO:2 . 2. The polynucleotide of claim 1 , wherein the second nucleic acid comprises a nucleotide sequence having at least 95% sequence identity with SEQ ID NO:3. 2. The polynucleotide of claim 1 , wherein the third nucleic acid comprises a nucleotide sequence having at least 95% sequence identity with SEQ ID NO:4. 2. The polynucleotide of claim 1 , wherein the fifth nucleic acid comprises a nucleotide sequence having at least 95% sequence identity with SEQ ID NO:5. A vector comprising the polynucleotide according to any one of claims 1-7 . 9. The vector of claim 8 , comprising a viral vector selected from lentiviral vectors, adeno-associated viral vectors and adenoviral vectors . A polypeptide encoded by the polynucleotide of any one of claims 1-7 . A cell comprising the polynucleotide of any one of claims 1-7 , or a protein encoded by said polynucleotide. 12. The cell of claim 11 , further comprising a polynucleotide encoding a chimeric antigen receptor (CAR), or a CAR protein. 13. The cell of claim 12 , which is a T cell, a CD8+ T cell, a CD4+ T cell, a cell derived from a CD8+ T cell or a cell derived from a CD4+ T cell . 12. The cell of claim 11 for use in a method of treating, suppressing or alleviating cancer in a subject. said method comprising:
(i) does not include co-administering cytokines to said subject, or
(ii) further comprising co-administering a cytokine to said subject;
To a subject to whom the dosage of the cytokine does not contain the polynucleotide according to any one of claims 1 to 7 or the protein encoded by the polynucleotide and is administered cells containing a chimeric antigen receptor (CAR) 15. Cells for use according to claim 14 , characterized in that they are lower than the dose of co-administered cytokines. 16. A cell for use according to claim 15 , wherein said cytokine is selected from IL-7, IL-15 and IL-21. 17. A cell for use according to claim 16 , wherein said cytokine comprises IL-21. 15. Cells for use according to claim 14 , wherein said cells are autologous cells of said subject and/or said subject is human . The cancer is colorectal cancer, breast cancer, ovarian cancer, lung cancer, pancreatic cancer, prostate cancer, malignant melanoma, kidney cancer, pancreatic cancer, brain tumor, glioblastoma, neuroblastoma, medulloblastoma 15. A cell for use according to claim 14 , comprising solid tumors such as , sarcoma, bone cancer, liver cancer; or non-solid tumors such as leukemia, multiple myeloma. A method of preparing a cell population comprising a chimeric antigen receptor (CAR) comprising:
(a) transducing a T cell with the polynucleotide of any one of claims 1-7 ;
(b) transducing said T cells with another polynucleotide encoding a chimeric antigen receptor (CAR); and (c) under conditions that stimulate activation and expansion of said transduced T cells. , culturing said T cells in a culture medium that does not contain exogenous cytokines. 21. The method of claim 20 , wherein said cytokine is selected from IL-7, IL-15 and IL-21.