Induction of p53 expression by neutralization of neuropilin-2 for the treatment of cancers
The present invention relates to the use of anti-human neuropilin-2 antibodies, or of ligands of human neuropilin-2 derived from these antibodies, for obtaining a medicament intended to increase p53 expression and to induce tumor cell apoptosis in the context of an anticancer treatment.
1. An anti-human neuropilin-2 antibody, characterized in that the binding thereof to tumour cells expressing human neuropilin-2 induces apoptosis of said tumour cells wherein the antibody is chosen from the following:
i. an antibody comprising the variable domain of the heavy chain and the variable domain of the light chain of the ITAC-BI antibody, said domains being respectively defined by the sequences SEQ ID NO: 2 and SEQ ID NO: 4;
ii. an antibody comprising the variable domain of the heavy chain and the variable domain of the light chain of the ITAC-B2 antibody, said domains being respectively defined by the sequences SEQ ID NO: 6 and SEQ ID NO: 8.
2. A polypeptide which binds to human neuropilin2 derived from an antibody as in claim 1 , characterized in that it comprises at least the CDR1, CDR2 and CDR3 of the heavy chain and the CDR1, CDR2 and CDR3 of the light chain of the ITAC-B1 antibody, wherein said CDRs are respectively defined by sequences SEQ ID NO: 9 to 14, or of the ITAC-B2 antibody, wherein said CDRs are respectively defined by sequences SEQ ID NO: 15 to 20.
3. The polypeptide according to claim 2 , characterized in that it is a humanized antibody.
4. A method of treating a tumor containing tumor cells which express human neuropilin-2 in a subject in of such treatment comprising administering an amount of the antibody of claim 1 effective to bind to human neuropilin-2 on the tumor cell.
5. The method of claim 4 wherein the amount of the antibody is effective to increase p53 expression in the tumor cell upon binding to human neuropilin-2.
6. The method of claim 4 wherein the amount of antibody is effective to induce apoptosis of the tumor cell upon binding to human neuropilin-2.
7. A method of treating a tumor containing tumor cells which express human neuropilin-2 in a subject in of such treatment comprising administering an amount of the polypeptide of claim 3 effective to bind to human neuropilin-2 on the tumor cell.
8. The method of claim 7 wherein the amount of the polypeptide is effective to increase p53 expression in the tumor cell upon binding to human neuropilin-2.
9. The method of claim 7 wherein the amount of polypeptide is effective to induce apoptosis of the tumor cell upon binding to human neuropilin-2.