Immunocytokines for tumour therapy with chemotherapeutic agents
Immunocytokine comprising cytokine, e.g. interleukin 2 (IL-2), conjugated to antibody against tumour neovasculature antigen, e.g. tenascin-C, for use in combination therapy with chemotherapeutic agent such as temozolomide. Use of immunocytokine and chemotherapy for treatment of tumours e.g. glioblastoma and other cancers.
1. A method of treating glioblastoma in an individual, comprising administering a chemotherapeutic agent and an immunocytokine to the individual, wherein the chemotherapeutic agent is temozolomide and wherein the immunocytokine comprises interieukin-2 (IL2) conjugated to an antibody molecule that binds domain A1 of tenasin-C large isoform, wherein the antibody molecule comprises an antibody-antigen binding site comprising a VH domain and a VL domain, the VH domain comprising:
a VH CDR1 of SEQ ID NO: 18 or a VH CDR1 of SEQ ID NO:5;
a VH CDR2 of SEQ ID NO: 6;
and a VH CDR3 of SEQ ID NO: 7;
and the VL domain comprising:
a VL CDR1 of SEQ ID NO:8;
a VL CDR2 of SEQ ID NO:9; and a VL CDR3 of SEQ ID NO:10.
2. A method according to claim 1 wherein the antibody molecule comprises an antibody-antigen binding site comprising the 4A1-F16 VH domain SEQ ID NO. 17 and the 4A1-F16 VL domain SEQ ID NO:4.
3. A method according to claim 1 , wherein the antibody molecule comprises an antibody-antigen binding site comprising the 4A1-F16 VH domain SEQ ID NO:2 and the 4A1-F16 VH domain SEC ID NO:4.
4. A method according to claim 1 , wherein the immunocytokine comprises IL2 conjugated to an scFv antibody molecule.
5. A method according to claim 1 , wherein treating the glioblastoma comprises retarding growth of the glioblastoma, reducing size of the glioblastoma or inhibiting regrowth of the glioblastoma in the individual.
6. A method according to claim 2 , wherein the immunocytokine comprises IL2 conjugated to an scFv antibody molecule.
7. A method according to claim 3 , wherein the immunocytokine comprises IL2 conjugated to an scFv antibody molecule.
8. A pharmaceutical composition for the treatment of glioblastoma comprising effective amounts of temozolomide and interleukin 2 conjugated to an antibody molecule that binds domain A1 of tenascin-C isoform, wherein the antibody molecule comprises an antibody-antigen binding site comprising a VH domain and a VL domain, the VH domain comprising:
a VH CDR1 of SEQ ID NO: 18 or a VH CDR1 of SEQ ID NO:5;
a VH CDR2 of SEQ ID NO: 6;
and a VH CDR3 of SEQ ID NO: 7;
and the VL domain comprising:
a VL CDR1 of SEQ ID NO: 8;
a VL CDR2 of SEQ ID NO:9; and a VL CDR3 of SEQ ID NO:10 in a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 wherein the immunocytokine comprises IL2 conjugated to an scFv antibody molecule.
10. The method of claim 1 , comprising administering the immunocytokine Lathe individual by intravenous injection.
11. The pharmaceutical composition of claim 8 , wherein the composition is formulated for intravenous injection of the interleukin 2 conjugated to the antibody molecule.
12. The pharmaceutical composition of claim 11 , wherein the composition is formulated for separate administration of the temozolomide and the antibody molecule.