Targeted amatoxin conjugate for the treatment of solid tumors

An amatoxin-linker construct

• for use in the manufacture of a binding moiety-toxin conjugate for the treatment of a solid tumor,
• wherein the amatoxin-linker construct has a formula selected from the group consisting of:
• and
• wherein said solid tumor is resistant to a binding moiety-toxin conjugate whose amatoxin according to formula (I) does not comprise an —OR4 substituent at 6′-position of the indol, wherein formula (I) is defined as
• R1 and R2 are each —OH
• R3 is NH2, or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety,
• R4 is H or a linker which carries a reactive group Y for linking said amatoxin to a target-binding moiety,
• R5 is absent or ═O,
• wherein R3 and R4 cannot be the same, and
• wherein the target-binding moiety is an antibody, antibody fragment, antibody-based binding protein, or an antibody mimetic, all of which retain target binding properties.