Use of herpes vectors for tumor therapy
Eliciting a systemic antitumor immune response can be efficacious for a patient who presents with or who is at risk of developing multiple metastatic tumors of a given cell type. To this end a pharmaceutical composition is employed that comprises a defective HSV vector, preferably containing an expressible nucleotide sequence encoding at least one immune modulator.
1. A method of eliciting a systemic antitumor immune response in a patient with or who is at risk of developing multiple metastatic tumors of a given cell type, comprising the step of inoculating a tumor in the patient with a pharmaceutical composition consisting essentially of:
(A) a herpes simplex virus (HSV) that infects tumor cells but that does not spread in normal cells, and
(B) a pharmaceutically acceptable vehicle for the virus,
wherein (i) the composition induces an immune response that is specific for the tumor cell type and that kills cells of the inoculated tumor and of a non-inoculated tumor, (ii) the herpes simplex virus is an HSV type-1 (HSV-1) virus, and (iii) the herpes simplex virus comprises one or more nucleotide sequences encoding GM-CSF.
2. The method of claim 1 , wherein the virus replicates in dividing cells and exhibits attenuated replication in non-dividing cells.
3. The method of claim 2 , wherein the virus is incapable of expressing both (i) a functional γ34.5 gene product and (ii) a ribonucleotide reductase.
4. The method of claim 3 , wherein the virus is a multi-gene mutant G207.
5. The method of claim 1 , wherein the virus is replication-defective.
6. The method of claim 5 , wherein the virus is a temperature-sensitive mutant.
7. The method of claim 6 , wherein the virus is an ICP4 mutant tsK.
8. The method of claim 1 , wherein the virus is conditionally replication-competent.
9. The method of claim 8 , wherein the virus is a mutant G92A.
10. The method of claim 1 , wherein the virus is of a vaccine strain.
11. The method of claim 1 , wherein the tumor cells are of a type selected from the group consisting of astrocytoma, oligodendroglioma, meningioma, neurofibroma, glioblastoma, ependymoma, Schwannoma, neurofibrosarcoma, and medulloblastoma.
12. The method of claim 1 , wherein the tumor cells are selected from the group consisting of melanoma cells, pancreatic cancer cells, prostate carcinoma cells, head and neck cancer cells, breast cancer cells, lung cancer cells, colon cancer cells, lymphoma cells, ovarian cancer cells, renal cancer cells, neuroblastomas, squamous cell carcinomas, medulloblastomas, hepatoma cells, mesothelioma cells, and epidermoid carcinoma cells.
13. The method of claim 1 , wherein the patient presents with multiple metastatic tumors.