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Immune Response to Brain Tumors

Together, primary brain tumor (originating in the brain) and metastatic brain tumors (spreading from other parts of the body) constitute the third leading cause of cancer deaths in young adults ages 20-39.

Among these brain tumors, malignant gliomas are the most common and aggressive.

Gliomas account for the majority of deaths due to primary neoplasms. Despite recent advances in treatment by combination surgery, radiotherapy, and chemotherapy, the average life expectancy of patients with gliomas remains low. One of the main factors leading to such poor prognosis is the fact that these tumors are able to grow within the brain without any significant impedance from the immune system. Although the immune system attempts to attack and remove the glioma, the T-cells aren’t able to sufficiently infiltrate the areas of tumor growth.

Furthermore, gliomas express a protein, FasL that, when in contact with immune cells, causes them to commit suicide. Recently, the Johns Hopkins Comprehensive Brain Tumor Center has shown that the expression of FasL by tumor cells is actually higher than in normal brain cells.

We hope that by inhibiting the expression of the FasL protein in brain tumors, it will be possible for the immune system to produce an adequate defense to eliminate the tumor.

Our lab is currently working towards developing methods to down regulate the expression of FasL in tumor cells and facilitate a more effective immune response towards these highly aggressive tumors. Through the incorporation of molecular techniques and animal cancer models we are developing viral based immuno-therapies that can be delivered directly to the site of tumor growth. By engineering retroviruses to deliver siRNA for FasL, it is possible to target tumor cells while leaving the normal cells of the brain unharmed. siRNA is a new technology that allows the highly specific inhibition of particular genes.

This work will allow us to better understand how tumor cells avoid attack by the immune system and also uncover new avenues for tumor vaccine development and improvement. Once established, we are confident that these methods will be applicable to a variety of different cancers types.

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