Immunotherapy targeting glioma stem cells--insights and perspectives.
BACKGROUND
Glioblastoma multiforme (GBM) is the most aggressive and lethal primary malignant brain tumor. Although progress has been made in current conventional therapies for GBM patients, the effect of these advances on clinical outcomes has been disappointing. Recent research into the origin of cancers suggest that GBM cancer stem cells (GSC) are the source of initial tumor formation, resistance to current conventional therapeutics and eventual patient relapse. Currently, there are very few studies that apply immunotherapy to target GSC.


METHODS
CD133, a cell surface protein, is used extensively as a surface marker to identify and isolate GSC in malignant glioma. We discuss biomarkers such as CD133, L1-cell adhesion molecule (L1-CAM), and A20 of GSC. We review developing novel treatment modalities, including immunotherapy strategies, to target GSC.


CONCLUSIONS
There are very few reports of preclinical studies targeting GSC. Identification and validation of unique molecular signatures and elucidation of signaling pathways involved in survival, proliferation and differentiation of GSC will significantly advance this field and provide a framework for the rational design of a new generation of antigen-specific, anti-GSC immunotherapy- and nanotechnology-based targeted therapyies. Combined with other therapeutic avenues, GSC-targeting therapies may represent a new paradigm to treat GBM patients.
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8361 West Third Street, Suite 800 E, Los Angeles, CA 90048, USA.
Zhenhua
Z
Li
Jang-Won
JW
Lee
Debraj
D
Mukherjee
Jianfei
J
Ji
Sunil P
SP
Jeswani
Keith L
KL
Black
John S
JS
Yu
D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D005909:Glioblastoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000639:trends; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D014408:Biomarkers, Tumor