title: Chimeric antigen receptors for treatment of glioblastoma: a practical review of challenges and ways to overcome them.
abstract: Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected niche within the blood-brain barrier and the heterogeneity of the cancer cells, which possess varying degrees of susceptibility to various common modalities of treatment. Over time, it is the tumor heterogeneity of GBM and the ability of the cancer stem cells to evolve in response treatment that renders the cancer refractory to conventional treatment. Therefore, research has increasingly focused on treatment that incorporates knowledge of GBM molecular biology to therapeutic strategies. One type of therapy that shows great promise is the area of T-cell immunotherapy to target GBM-specific tumor antigens. One attractive strategy is to use T cells that have undergone genetic modification to express a chimeric antigen receptor capable of interacting with tumor antigens. In this article, we will review chimeric antigen receptor T-cell therapy, their advantages, drawbacks, challenges facing their use and how those challenges may be overcome.
authors: Brain Tumor Laboratory, Roger Williams Medical Center, Providence, RI, USA.|Department of Neurosurgery, Rhode Island Hospital, Providence, RI, USA.
authors: S
authors: S
authors: Sengupta
authors: Department of Pathology, Rhode Island Hospital, Providence, RI, USA.
authors: G
authors: G
authors: Mao
authors: Department of Neurosurgery, Rhode Island Hospital, Providence, RI, USA.
authors: Z S
authors: ZS
authors: Gokaslan
authors: Brain Tumor Laboratory, Roger Williams Medical Center, Providence, RI, USA.|Department of Neurosurgery, Rhode Island Hospital, Providence, RI, USA.
authors: P
authors: P
authors: Sampath
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D002465:Cell Movement / Q000276:immunology; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D016896:Treatment Outcome; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins