Use of antibody against o-acetylated gd2 ganglioside to improve the therapeutic potential of drugs
AssigneesOgd2 Pharma, Universite De Nantes, Centre National de la Recherche Scientifique (CNRS), Institut National De La Sante Et De La Recherche Medicale (Inserm), Institut De Cancerologie De L'ouest
InventorsStéphane BIRKLE, Julien FLEURENCE, Sébastien FARAJ, Jean-Marc LE DOUSSAL, Denis COCHONNEAU, Mickaël TERME, Brigitte ASSOULINE
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Abstract
Disclosed is a method for delivery of an anti-cancer agent into a cell expressing the OAcGD2 ganglioside by using an antibody recognizing the OAcGD2 ganglioside.
Claims23
A method for delivery of an anti-cancer agent into a cell expressing the OAcGD2 ganglioside comprising contacting the cell with at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, in an amount and concentration effective to enhance uptake of the anti-cancer agent by the cell, wherein the antibody causes permeability defects within the cell membrane.
A composition for delivery of an anti-cancer agent into a cell, expressing the OAcGD2 ganglioside comprising:
- (i) at least one anti-cancer agent, and (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, wherein the at least one antibody recognizing the OAcGD2 ganglioside enhances the uptake of the at least one anti-cancer agent by the tumor cell.
A multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, for use in the selective delivery into a cell expressing the OAcGD2 ganglioside of at least one anti-cancer agent to treat and/or to prevent cancer.
A method of increasing the efficacy of a cancer expressing the OAcGD2 ganglioside treatment comprising an anti-cancer agent, comprising administering to a patient in need thereof an effective amount of a composition comprising:
- (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof.
A method of increasing sensitivity to an anti-cancer agent in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising:
- (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof.
A method of preventing or delaying development of cancer resistant to an anti-cancer agent in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising:
- (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof.
An in vitro/ex vivo method of identifying synergistic combination of (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons and, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof comprising the steps of:
- a) incubating primary tumor cells or cancer cell lines cells expressing the O-acetylated form of GD2 ganglioside in vitro with a composition comprising at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons and, (ii) at least one antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, and
- b) measuring the CI50 index according to the method as disclosed by Chou and Talalay, wherein a CI50 below 1 is indicative of synergism.
A kit suitable for treating cancer expressing OAcGD2 ganglioside comprising (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, and a functional fragment or a derivative thereof.
A method for enhancing intracellular uptake of an anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons in a cell expressing the O-acetylated form of GD2 ganglioside, comprising administering an effective amount of a multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof.
A method of treating a refractory or relapsed cancer in a patient suffering from a cancer expressing the OAcGD2 ganglioside, comprising administering to a patient in need thereof an effective amount of a composition comprising:
- (i) at least one anti-cancer agent having a molecular mass ranging from 100 Daltons to 200,000 Daltons, (ii) at least one multimeric antibody recognizing the OAcGD2 ganglioside, a functional fragment or a derivative thereof, wherein said cancer is refractory to or is in relapse after a first line cancer treatment comprising one or more anti-cancer agent selected from the group consisting of alkylating agents, antimetabolites, anti-tumor antibiotics, topoisomerase inhibitors, mitotic inhibitors, tyrosine kinase inhibitors and nucleoside analogs.
Dependencies are inferred from the claim text.