1045. Targeted Elimination of the Brain Tumor Initiating Cell Population with Adoptively Transferred T Cells

Abstract

Top of pageAbstract The cancer stem cell hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties, which include the ability to proliferate, self-renew, and to exhibit multi-lineage differentiation. Human brain tumors have been shown to consist of a subset of cells identified by the cell- surface marker CD133 that exhibit stem cell-like properties, and which can drive tumor formation. We have isolated and expanded the CD133+ cancer stem cell (CSC) population from primary human brain tumors and have demonstrated that these cells do exhibit stem cell like properties: 1) grow in neurophere-like clusters in and EGF and FGF dependent manner; 2) self-renew in vitro in a CD133- dependent manner to reform secondary neurospheres 3) express stem cell markers such as SOX2, OCT3/4, and Nanog; 4) differentiate to express lineage specific markers such as GFAP; and 5) form tumors in nod-SCID mice with implantation of as few as 100 cells. These low passage primary CSC neurosphere cultures form highly invasive tumors in nod-scid mice. We are currently investigating the immunobiology of targeting CSC xenografts with CTLs engineered to target and eliminate IL13R|[alpha]|2+ glioma cells.