Production method for t cells or nk cells, medium for culturing t cells or nk cells, method for culturing t cells or nk cells, method for maintaining undifferentiated state of undifferentiated t cells, and growth-accelerating agent for t cells or nk cells

A culture medium for culturing T cells or NK cells, comprising a bisbenzylisoquinoline alkaloid represented by the following formula (X-1) or formula (X-2) or a compound resulting from cleavage of one ether bond thereof or a pharmaceutically acceptable salt thereof:

• R1 and R′1 are each independently H or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms,
• R2, R′2, R3, R′3, R4, R′4, R5, and R′5 are each independently H, acyl, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R2 and R3, R4 and R5, R′2 and R′3, or R′4 and R′5 together represent O or S,
• R6, R′6, R7, and R′7 are each independently H, acyl, or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R6 and R7 or R′6 and R′7 together represent O or S, and
• X1, X2, X3, and X4 may be the same or different, and are each independently H, hydroxy, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, alkoxy, acyloxy, or sulfonyloxy, and each may further have a substituent, n1 and n3 are each independently an integer of 0 to 3, n2 and n4 are each independently an integer of 0 to 4, and these may be linked to each other to form a ring.

A method for culturing T cells or NK cells, comprising culturing T cells or NK cells in a culture medium containing a bisbenzylisoquinoline alkaloid represented by the following formula (X-1) or formula (X-2) or a compound resulting from cleavage of one ether bond thereof or a pharmaceutically acceptable salt thereof:

• R1 and R′1 are each independently H or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms,
• R2, R′2, R3, R′3, R4, R′4, R5, and R′5 are each independently H, acyl, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R2 and R3, R4 and R5, R′2 and R′3, or R′4 and R′5 together represent O or S,
• R6, R′6, R7, and R′7 are each independently H, acyl, or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R6 and R7 or R′6 and R′7 together represent O or S, and
• X1, X2, X3, and X4 may be the same or different, and are each independently H, hydroxy, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, alkoxy, acyloxy, or sulfonyloxy, and each may further have a substituent, n1 and n3 are each independently an integer of 0 to 3, n2 and n4 are each independently an integer of 0 to 4, and these may be linked to each other to form a ring.

A method for maintaining an undifferentiated state of undifferentiated T cells, comprising culturing undifferentiated T cells in a culture medium containing a bisbenzylisoquinoline alkaloid represented by the following formula (X-1) or formula (X-2) or a compound resulting from cleavage of one ether bond thereof or a pharmaceutically acceptable salt thereof:

• R1 and R′1 are each independently H or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms,
• R2, R′2, R3, R′3, R4, R′4, R5, and R′5 are each independently H, acyl, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R2 and R3, R4 and R5, R′2 and R′3, or R′4 and R′5 together represent O or S,
• R6, R′6, R7, and R′7 are each independently H, acyl, or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R6 and R7 or R′6 and R′7 together represent O or S, and
• X1, X2, X3, and X4 may be the same or different, and are each independently H, hydroxy, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, alkoxy, acyloxy, or sulfonyloxy, and each may further have a substituent, n1 and n3 are each independently an integer of 0 to 3, n2 and n4 are each independently an integer of 0 to 4, and these may be linked to each other to form a ring.

A growth promoter for T cells or NK cells, comprising a bisbenzylisoquinoline alkaloid represented by the following formula (X-1) or formula (X-2) or a compound resulting from cleavage of one ether bond thereof or a pharmaceutically acceptable salt thereof as an active ingredient:

• R1 and R′1 are each independently H or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms,
• R2, R′2, R3, R′3, R4, R′4, R5, and R′5 are each independently H, acyl, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R2 and R3, R4 and R5, R′2 and R′3, or R′4 and R′5 together represent O or S,
• R6, R′6, R7, and R′7 are each independently H, acyl, or straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, and the alkyl may be interrupted by an O, N, or S heteroatom, or R6 and R7 or R′6 and R′7 together represent O or S, and
• X1, X2, X3, and X4 may be the same or different, and are each independently H, hydroxy, straight-chain or branched-chain alkyl having 1 to 10 carbon atoms, alkoxy, acyloxy, or sulfonyloxy, and each may further have a substituent, n1 and n3 are each independently an integer of 0 to 3, n2 and n4 are each independently an integer of 0 to 4, and these may be linked to each other to form a ring.