AMATOXIN-ARMED THERAPEUTIC CELL SURFACE BINDING COMPONENTS DESIGNED FOR TUMOUR THERAPY

摘要

The invention relates to tumour therapy. In one aspect, the present invention relates to conjugates of a toxin and a target-binding moiety, e.g. an antibody, which are useful in the treatment of cancer. In particular, the toxin is an amatoxin, and the target-binding moiety is preferably directed against tumour-associated antigens. In particular, the amatoxin is conjugated to the antibody by linker moieties. In particular the linker moieties are covalently bound to functional groups located in positions of the amatoxin proved as preferred positions for the attachment of linkers with respect to optimum antitumor activity. In a further aspect the invention relates to pharmaceutical compositions comprising such target-binding moiety toxin conjugates and to the use of such target-binding moiety toxin conjugates for the preparation of such pharmaceutical compositions. The target-binding moiety toxin conjugates and pharmaceutical compositions of the invention are useful for the treatment of cancer.

主权项

1. A target-binding moiety toxin conjugate comprising:
(i) a target-binding moiety; (ii) at least one amatoxin; and (iii) optionally a linker L1; wherein the at least one amatoxin is connected to said target-binding moiety via the γ′ C-atom of amino acid 1 of said amatoxin or, if said optional linker is present, the at least one amatoxin is connected to the linker L1 via the γ′ C-atom of amino acid 1 of said amatoxin and said linker is connected to said target binding moiety, and wherein the target binding moiety is an antibody or antigen-binding fragment thereof.