Research Plan Summary: Qingyang (Kristy) Yuan

IL-12 Secreting adipose-derived mesenchymal stem cells as immunotherapy against cancer stem cell derived glioblastoma multiforme

The overall aim of this project is to assess the anti-tumor activity of IL-12 secreting human adipose-derived mesenchymal stem cells (IL-12-hAMSCs) against glioblastoma multiforme (GBM). Specifically, we will describe how IL-12-hAMSCs

1) affect the immune effectors of the anti-tumor response in vitro by using flow cytometry to measure CD4+, CD8+, and NK T cells after co-culture with T lymphocytes and IFN-gamma after co-culture with peripheral mononuclear cells;

2) behave amongst glioma cells in vitro by assessing the ability for multi-lineage differentiation before and after co-culture with GBM;

3) amount an anti-glioma response in mouse brains in vivo by immunohistochemical assays of hAMSC tracking, T cell infiltration, cytotoxic lysis assays, and survival follow-up.
We hypothesize that IL-12-hAMSCs will upregulate immune effectors in vitro, lose their pluripotency upon interacting with GBM, and induce an anti-tumor effect and survival benefit in vivo after selectively migrating to the GBM site. This project is significant in that: we will be the first to test the efficacy of genetically modified hAMSCs as therapeutic vectors against GBM; we will characterize the controversial fate of hAMSCs when interacting with GBM; we will use a cancer stem cell derived glioma line to mimic the nature of high grade gliomas and a NOG (NOD/Shi-scid IL2R-gamma null) murine host for high levels of immune reconstitution with human hematopoeitic stem cells. This study is critical in justifying the use of IL-12-hAMSCs for future clinical trials of GBM treatment and of adipose-derived mesenchymal stem cells as vectors for cancer therapy.