JPWO2019246563A5 - - Google Patents

Claims (20)

A protein comprising a transmembrane domain of the α chain of an interleukin-7 receptor having one or more modifications, wherein the transmembrane domain having one or more modifications is the sequence of SEQ ID NO: 2, 4, 6 or 8. Has a protein. The protein according to claim 1, further comprising the intracellular domain of the α chain of the interleukin-7 receptor. The protein according to claim 2, wherein the intracellular domain comprises the sequence of SEQ ID NO: 45. The protein according to claim 1, further comprising the extracellular domain of the α chain of the interleukin-7 receptor. The protein according to claim 4, wherein the extracellular domain comprises the sequence of SEQ ID NO: 11. Extracellular interleukin-15 domain and
The extracellular sushi domain derived from the α chain of the interleukin-15 receptor,
The protein according to claim 1, further comprising. The protein of claim 6, wherein the extracellular interleukin-15 domain comprises the sequence of SEQ ID NO: 22 or SEQ ID NO: 24. The protein according to claim 6, wherein the extracellular shisi domain of the α chain of the interleukin-15 receptor comprises SEQ ID NO: 36 or SEQ ID NO: 37. A nucleic acid encoding the protein according to claim 1. A vector containing the nucleic acid according to claim 9. The vector according to claim 10, further comprising a promoter operably linked to the nucleic acid and optionally an enhancer sequence operably linked to the nucleic acid. The vector according to claim 10, further comprising a sequence encoding a chimeric antigen receptor that specifically binds to a tumor antigen. The tumor antigens are Glypican-3, BCMA, MAGE, MUC16, CD19, WT-1, CD22, LI-CAM, ROR-1, CEA, 4-1BB, ETA, 5T4, adenocarcinoma antigen, α-fetoprotein (AFP). , BAFF, B lymphoma cells, C242 antigen, CA-125, carbonate dehydration enzyme 9 (CA-IX), C-MET, CCR4, CD152, CD20, CD125, CD200, CD221, CD23 (IgE receptor), CD28, CD30. (TNFRSF8), CD33, CD4, CD40, CD44 v6, CD51, CD52, CD56, CD74, CD80, CEA, CNT0888, CTLA-4, DR5, EGFR, EpCAM, CD3, FAP, fibronectin extra domain-B, folic acid receptor 1, GD2, GD3 ganglioside, glycoprotein 75, GPNMB, HER2 / neu, HGF, human scattering factor receptor kinase, IGF-1 receptor, IGF-I, IgG1, IL-13, IL-6, insulin-like growth factor I Receptor, Integulin α5β1, Integrin ανβ3, MORAb-009, MS4A1, MUC1, Mutin CanAg, N-glycolylneuraminic acid, NPC-1C, PDGF-R a, PDL192, phosphatidylserine, prostate cancer cells, RANKL, RON , SCH 900105, SDC1, SLAMF7, TAG-72, Tenesin C, TGFβ2, TGF-β, TRAIL-R1, TRAIL-R2, Tumor Antigen CTAA16.88, VEGF-A, VEGFR-1, VEGFR2 and Vimentin. The vector according to claim 12, which is selected. 4-1BB, CD27, OX40, CD40, CD28, GITR, CD2, CD5, ICAM-1, CD11a, Lck, TNFR-I, TNFR-II, FasR, CD30, ICOS, LIGHT, NKG2C , B7-H3, DAP- 10. The vector of claim 10, comprising a sequence encoding a chimeric antigen receptor comprising one or more co-stimulating signaling domains selected from the group consisting of 10 and DAP-12. The vector according to claim 10, which is a lentiviral vector or an adenoviral vector. A mammalian cell comprising the vector according to claim 10. The mammalian cell according to claim 16, which is an immune cell. 17. The mammal according to claim 17, wherein the immune cells are selected from the group consisting of CD4 + T cells, CD8 + T cells, B cells, monospheres, natural killer cells, dendritic cells, macrophages, regulatory T cells and helper T cells. cell. A pharmaceutical composition comprising the vector of claim 10 and a pharmaceutically acceptable carrier. The pharmaceutical composition comprising the mammalian cell according to claim 16.