Biotechnology - A new immunological treatment for malignant brain tumors (TASMC)
The tumor: Malignant primary brain tumors and especially the highly malignant Glioblastoma Multiforme (GBM) are fatal within months of diagnosis in almost all patients. There are more than 20,000 patients in the US and approximately 200,000 patients worldwide that are diagnosed annually with malignant brain tumors. Although brain tumors constitute 1.4% of new cancers diagnosed, due to their dismal prognosis and relatively early age of onset they represents 2.4% of cancer deaths and 7% of person-years of life lost (PYLL) due to cancer (fourth after lung, colon and breast cancer). In children, brain tumors are the second most prevalent cancer after leukemia, constituting 17% of new cancers. Primary brain tumors are the leading cause of cancer-related death in children.
Even after aggressive surgical resection followed by adjuvant therapy such as radiotherapy and chemotherapy, almost all patients diagnosed with high-grade gliomas succumb to their disease. The median life expectancy of a patient with GBM is less than 12 months [Lorico A et al, 2008, Can. Gene Ther]. Surgery has little or no beneficial effect on survival [Hess KR. 1999. J Neurooncol]; even removal of a brain hemisphere is insufficient to save GBM patients [Demuth T. et al, 2004. J Neurooncol]. Treatment of these malignancies is particularly problematic due to the sensitivity of the collateral brain tissue to disruption during surgical excision and to the toxicity of many therapeutic agents [Mitchel DA et al, 2008, Immunol Rev]. Current standard treatments do not extend the survival of patients by more than ten weeks [Cohen MH. et al, 2005. Clin Cancer Res]
Directing the immune system to fight brain tumors: Immunological therapy (immunotherapy) harnesses the immune system to combat cancer. Gliomas, the most prevalent of malignant brain tumors, are highly infiltrative, spreading to areas inside the brain that are distant from their initial location. Unlike other treatments that kill tumor cells mostly in their initial location, immunotherapy generates tumor specific immune cells that can locate and kill even small, unidentified metastatic lesions located inside the brain. Unlike chemotherapy and irradiation, even aggressive immunotherapeutic approaches cause little or no collateral damage to surrounding brain tissue.
We have developed a new approach to immunotherapy, and have successfully demonstrated its efficacy in treating highly aggressive primary brain tumors in rats. In the Fischer rat GBM model ('F98'), a single immunization led to an increased mean survival time of about 300% and 30% of the treated rats were completely cured of their tumors. These results were shown in more than ten independent experiments. An improved protocol featuring multiple immunizations enhanced survival; all treated rats remained alive even after 6 months, while all untreated animals died by 5 weeks following inoculation with the brain tumors.
To corroborate these results, we employed another model - the Lewis rat 'CNS-1' astrocytoma (a type of glioma). In this model, we showed in several experiments 80-100% cure rates using various immunization protocols. All in-vivo experiments in both models showed similar, highly significant results, unprecedented in the published scientific literature regarding these malignant tumor models
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