Use of monoclonal antibodies specific to the O-acetylated form of GD2 ganglioside for the treatment of certain cancers

摘要

The monoclonal antibodies that only recognize the O-acetylated form of the GD2 ganglioside, or fragments of the antibody, for the diagnosis and the treatment of cancers in which the cells express the O-acetylated GD2, the antibody or the fragment recognizing the O-acetylated GD2 molecules expressed by the tumoral cells and not recognizing the GD2 molecules expressed at the surface of the peripheral nerves, in order to increase the specificity of the diagnosis and reduce the toxicity of the treatments. Also artificially modified antibodies advantageously used for treating and diagnosing cancers in which the cells express the O-acetylated GD2.

主权项

1. A method for the treatment of cancers expressing the O-acetylated form of GD2 ganglioside selected from the group consisting of neuroblastomas, lymphomas, melanomas, glioblastomas and small cell lung cancers, said method comprising administering to a patient in need thereof an antibody or a fragment thereof that specifically binds to O-acetylated GD2 ganglioside and which is coupled to a biological toxic molecule (BTM), wherein said antibody or a fragment thereof has the complementarity-determining regions of the H chain variable region comprising amino acid sequences represented in SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4 and has the complementarity-determining regions of the L chain variable region comprising amino acid sequences represented in SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, wherein said antibody has an affinity of at least ten times lower for the non O-acetylated form of GD2 ganglioside and wherein an effective amount of said antibody or a fragment thereof coupled to a biological toxic molecule (BTM) provides cytotoxic activity against said cancer cells.