Tumors In NOD-SCID Mice Research Articles

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

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.

Rapid tumor formation of human T-cell leukemia virus type 1-infected cell lines in novel NOD-SCID/gammac(null) mice: suppression by an inhibitor against NF-kappaB.

We established a novel experimental model for human T-cell leukemia virus type 1 (HTLV-1)-induced tumor using NOD-SCID/gammac(null) (NOG) mice. This model is very useful for investigating the mechanism of tumorigenesis and malignant cell growth of adult T-cell leukemia (ATL)/lymphoma, which still remains unclear. Nine HTLV-1-infected cell lines were inoculated subcutaneously in the postauricular region of NOG mice. As early as 2 to 3 weeks after inoculation, seven cell lines produced a visible tumor while two transformed cell lines failed to do so. Five of seven lines produced a progressively growing large tumor with leukemic infiltration of the cells in various organs that eventually killed the animals. Leukemic cell lines formed soft tumors, whereas some transformed cell lines developed into hemorrhagic hard tumors in NOG mice. One of the leukemic cell lines, ED-40515(-), was unable to produce visible tumors in NOD-SCID mice with a common gamma-chain after 2 weeks. In vivo NF-kappaB DNA binding activity of the ED-40515(-) cell line was higher and the NF-kappaB components were changed compared to cells in vitro. Bay 11-7082, a specific and effective NF-kappaB inhibitor, prevented tumor growth at the sites of the primary region and leukemic infiltration in various organs of NOG mice. This in vivo model of ATL could provide a novel system for use in clarifying the mechanism of growth of HTLV-1-infected cells as well as for the development of new drugs against ATL.