Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy

By Christine E. Brown, D. Alizadeh, R. Starr, L. Weng, Jamie R Wagner, A. Naranjo, J. Ostberg, M. S. Blanchard, Julie Kilpatrick, Jennifer Simpson and 12 more. New England Journal of Medicine, 2016

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SUMMARY A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes — infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy.

Subfields: Biomedical Engineering, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/31daf0bac82863c7fc605c7dd03191120b87436c

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Citations in the corpus

Tumor Antigen Escape from CAR T-cell Therapy. (2018, background): “Furthermore, loss of target antigen has also been observed in a patient with multiple myeloma treated with a CAR targeting BCMA (29) as well as in patients with glioblastoma multiforme who were treated with CARs targeting either EGFRvIII (30) or IL13Rα2 (31).”
Immunotherapy for glioma: current management and future application. (2020, neutral): “This therapeutic strategy was evaluated by a phase I clinical trial, in which complete remission was detected in a single patient according to the report [134].”
Clinical and Biologic Correlates of Neurotoxicity Associated with CAR T Cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia (B-ALL) (2018, result): “However, our data suggest that CAR infiltration into the CSF per se is not responsible for severe neurologic symptoms, and this finding is also consistent with the absence of neurotoxicity in 1 patient after receiving intrathecal and intratumoral administration of CAR T cells for recurrent glioblast”
The microenvironmental landscape of brain tumors (2017, background): “While there is certainly reason for optimism in targeting and/or re-educating the TME in brain malignancies, as evidenced by encouraging initial results with chimeric antigen receptor (CAR) T cell therapy in a glioma patient case study (Brown et al., 2016), we nonetheless have considerable progress ”
Gene therapy clinical trials worldwide to 2017: An update (2018, background): “The number of reports targeting solid tumours such as glioblastoma, which are more challenging to treat, is also increasing.(31-33)”
Engineering strategies to overcome the current roadblocks in CAR T cell therapy (2019, background): “For example, zetakine CARs comprising cytokines fused to intracellular signalling domains, such as those targeting IL-13 receptor α2 (IL-13Rα2) via membrane-tethered IL-13 linked to the intracellular 4-1BB and CD3ζ domains, have been tested in clinical studies 27 .”
CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment (2019, background): “(42) showed tumor regression induced by T cells expressing a 4-1BBζ IL13Rα2 CAR in a patient with glioblastoma.”