Targeting Human Glioma Stem Cells via Dendritic Cells

Kavita M. Dhodapkar, M.D.

Yale University School of Medicine

Funded in June, 2010: $200000 for 3 years


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Harnessing the innate immune system’s abilities to recognize the cells that drive tumor development

Investigators will attempt to strengthen the ability of innate immune cells to catalyze an attack against deadly human brain tumors.

Glioma brain tumors are rapidly lethal, causing death with a year or two. They are not currently treatable. Recent evidence indicates that a small subpopulation of the tumor’s cells, called “cancer stem cells,” is responsible for the tumor’s growth.  The cancer stem cells produce a protein, called SOX2, which appears to be important for their survival. The Yale investigators showed that by inhibiting SOX2 in tumor tissue surgically removed from glioma patients, they could suppress tumor growth.  They now hypothesize that they can harness tumor immunity by strengthening the ability of innate immune cells, called dendritic cells, to recognize SOX2 and present that information to specific immune T cells so that they will travel to the brain and attack the tumor stem cells.

To test this approach, they will first optimize how tumor patients’ dendritic cells in tissue samples studied in the laboratory present the SOX2 peptides to these specific immune T cells (called CD4 and CD8 T cells). Thereafter, they will translate their findings into efforts to develop an effective immunotherapy that is designed to strengthen the capacity of a patient’s immune system to successfully kill the tumor by inhibiting the tumor cells’ ability to proliferate and grow.

Significance:  This approach could ultimately result in the development of a therapeutic vaccine against glioma.