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Glioblastoma stem cells and stem cell-targeting immunotherapies

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Abstract

Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM.

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Acknowledgments

S.H.C. is the Tashia and John Morgridge Faculty Scholar of the Children’s Health Research Institute at Stanford, and the Ty Louis Campbell Foundation St. Baldrick’s Scholar. We would like to thank the Ludwig Center for Cancer Stem Cell Research and Medicine, the Stanford University School of Medicine Medical Scholars Research Program, the American Brain Tumor Association, Alex’s Lemonade Stand Foundation for Childhood Cancer, the St. Baldrick’s Foundation, the CureSearch for Children’s Cancer Foundation, and the Children’s Health Research Institute at Stanford for their support in the preparation of this manuscript. We would like to thank Sharareh Gholamin, M.D., Suzana A. Kahn, P.h.D., and Bahauddeen Alrfaei, Ph.D. for their insightful suggestions and discussion in the preparation of this review.

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    1. Division of Pediatric Neurosurgery, Department of Neurosurgery, Lucile Packard Children’s Hospital, Stanford University School of Medicine, 300 Pasteur Drive R211, Stanford, CA, 94305, USA

      Rogelio Esparza, Tej D. Azad, Abdullah H. Feroze, Siddhartha S. Mitra & Samuel H. Cheshier

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    Rogelio Esparza and Tej D. Azad have contributed equally to this work.

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    Esparza, R., Azad, T.D., Feroze, A.H. et al. Glioblastoma stem cells and stem cell-targeting immunotherapies. J Neurooncol 123, 449–457 (2015). https://doi.org/10.1007/s11060-015-1729-x

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