Treatment of brain cancers using central nervous system mediated gene transfer of monoclonal antibodies
The invention provides methods to inhibit or treat brain cancers by locally inhibiting expression or activity of growth factors or growth factor receptors.
1. A method of inhibiting glioblastoma, a glioma or a glial tumor in a human, comprising: intracranially or intracisternally administering to the human, during or after resection of the glioblastoma, glioma or glial tumor, a composition comprising an effective amount of a recombinant adeno-associated virus (rAAV) comprising:
i) an expression vector encoding an antibody directed against vascular endothelial growth factor (VEGF), wherein the antibody comprises SEQ ID NO:4 and SEQ ID NO:5; or ii) an expression vector encoding an antibody directed against epidermal growth factor receptor (EGFR), wherein the antibody comprises SEQ ID NO:8 and SEQ ID NO:9, wherein the rAAV comprises an AAVrh10 capsid.
2. The method of claim 1 wherein the amount is effective to reduce tumor volume or blood vessel density.
3. The method of claim 1 wherein the antibody that is expressed in the central nervous system of the mammal comprises two heavy chains and two light chains.
4. The method of claim 1 wherein the human has glioblastoma, a glial tumor, an astrocytoma, grade 1 glioma, grade 2 glioma, an oligodendroglioma, a neurocytoma, a dysplastic neuroepithelial tumor, a primitive neuroectodermal tumor, or a ganglioneuroma.
5. The method of claim 1 wherein the antibody is a chimeric or humanized antibody.
6. The method of claim 1 wherein the expression vector encodes the anti-VEGF antibody.
7. The method of claim 1 wherein the expression vector encodes the anti-EGFR antibody.
8. The method of claim 7 wherein the antibody binds to EGFRVIII.
9. The method of claim 1 wherein the composition does not include a permeation enhancing agent.
10. The method of claim 1 wherein the administration occurs during cancer resection.
11. The method of claim 1 wherein the human has glioblastoma.
12. The method of claim 1 wherein the administration is via a cannula or needle.
13. The method of claim 1 wherein the human has glioblastoma and the rAAV is intracranially administered.
14. The method of claim 1 wherein the human has glioblastoma and the rAAV is intracisternally administered.