JP-2022514393-A5 -

Dates

Publication Date

20221219

Application Date

20191220

Description

[Invention 1001]NK cell differentiation medium containing pyrimidoindole compounds.[Invention 1002]An NK cell differentiation medium according to the present invention 1001, wherein the pyrimidoindole compound is UM171 or UM729.[Invention 1003]An NK cell differentiation medium according to the present invention 1001 or 1002, further comprising a basal medium.[Invention 1004]An NK cell differentiation medium according to the present invention 1003, further comprising one or more of SCF, FLT3L, IL-2, IL-3, IL-15, or IL-7.[Invention 1005]An NK cell differentiation medium according to any of the present invention 1001 to 1004, which is not acclimatized by contact with stromal cells or stromal cell substitutes.[Invention 1006]An NK cell differentiation medium according to any of the invention 1001 to 1005, which does not contain an aromatic hydrocarbon receptor antagonist.[Invention 1007]A serum-free NK cell differentiation medium according to any of the invention's 1001 to 1006.[Invention 1008]An NK cell differentiation medium according to any of the present invention 1001 to 1007, for differentiating NK progenitor cells.[Invention 1009]An NK cell differentiation medium according to the present invention 1008, wherein NK progenitor cells are isolated from or derived from a primary sample.[Invention 1010]An NK cell differentiation medium according to the present invention 1008 or 1009, wherein the NK progenitor cells are derived from pluripotent stem cells.[Invention 1011]The NK cell differentiation medium of the present invention 1010, wherein the pluripotent stem cells are induced pluripotent stem cells.[Invention 1012]A method for differentiating cells into NK cells,The step of providing a population of NK progenitor cells, as well as;The step of contacting a population of cultured NK progenitor cells with any of the culture media from 1001 to 1011 of the present invention for a concentration and duration sufficient to produce NK cells.Methods that include...[Invention 1013]The method of the present invention 1012, wherein the population of NK progenitor cells is homogeneous or heterogeneous with respect to phenotypic markers.[Invention 1014]The method of the present invention 1013, wherein the phenotypic marker is CD7.[Invention 1015]The method of the present invention 1013 or 1014, wherein the phenotypic marker is CD5.[Invention 1016]A method of the present invention 1012 to 1015, wherein the frequency of NK cell appearance increases during the contact stage.[Invention 1017]A method of the present invention 1012 to 1016, wherein the number of NK cells increases during the contact step.[Invention 1018]Any method 1012 to 1017 of the present invention, wherein the frequency or number of appearances of a population of NK progenitor cells increases or decreases during the contact step.[Invention 1019]Any method 1012 to 1018 of the present invention, wherein neither stromal cells nor stromal cell substitutes are present in the supplying and contacting stages.[Invention 1020]Any method of the present invention 1012 to 1019, wherein an aromatic hydrocarbon acceptor antagonist is not present in the step of providing or the step of contacting.[Invention 1021]A method according to any one of the present invention 1012 to 1020, wherein the concentration of the pyrimidoindole compound is 10 nM to 3 μM.[Invention 1022]The method of any of the present invention 1012 to 1021, wherein the aforementioned period is at least one week.[Invention 1023]The method of the present invention 1022, wherein the aforementioned period is approximately two weeks.[Invention 1024]A method according to any of invention 1012 to 1023, wherein NK cells express CD56.[Invention 1025]A method according to any of the present invention 1012 to 1024, wherein NK cells are cytotoxic.[Invention 1026]A method according to any of items 1012 to 1025 of the present invention, wherein the population of NK progenitor cells is derived from a primary sample.[Invention 1027]A method according to any of items 1012 to 1025 of the present invention, wherein a population of cells is isolated from a primary sample.[Invention 1028]The method of the present invention 1027, wherein the primary sample is an umbilical cord blood sample, a bone marrow sample, or a peripheral blood sample.[Invention 1029]A method according to any one of the present invention 1012 to 1025, wherein a group of cells differentiates from pluripotent stem cells. Other features and advantages of the present invention will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples are provided merely as illustrations, while illustrating preferred embodiments of the present invention, for various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.