Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antig...

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Bibliographic Details
Published in:The New England journal of medicine Vol. 390; no. 14; pp. 1290 - 1298
Main Authors: Choi, Bryan D., Gerstner, Elizabeth R., Frigault, Matthew J., Leick, Mark B., Mount, Christopher W., Balaj, Leonora, Nikiforow, Sarah, Carter, Bob S., Curry, William T., Gallagher, Kathleen, Maus, Marcela V.
Format: Journal Article
Language:English
Published: United States Massachusetts Medical Society 11.04.2024
Series:Brief Report
Subjects:
Allergy
Antigens
Biopsy
Brain cancer
Brain Tumor
Catheters
CD8-Positive T-Lymphocytes - metabolism
Chemotherapy
Chimeric antigen receptors
Clinical outcomes
Epidermal growth factor receptors
ErbB Receptors - antagonists & inhibitors
ErbB Receptors - genetics
ErbB Receptors - metabolism
Genetics
Genetics General
Glioblastoma
Glioblastoma - pathology
Glioblastoma - therapy
Glioma
Hematology
Humans
Immunology
Immunotherapy
Immunotherapy, Adoptive - adverse effects
Lymphocytes
Lymphocytes T
Magnetic resonance imaging
Neoplasm Recurrence, Local - therapy
Neurology
Neuroscience
Neurosurgery
Oncology
Radiation
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - therapeutic use
Receptors, Chimeric Antigen - therapeutic use
T-Cells
Teams
Toxicity
Treatments in Oncology
Tumors
ISSN:0028-4793, 1533-4406, 1533-4406
Online Access:Get full text
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Summary:In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell–engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants. (Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number, NCT05660369 .) A novel CAR T-cell therapy directed at EGFRvIII with a secretable EGFR T-cell engager produced rapid responses in three patients with recurrent glioblastoma, but the responses were transient in two of the three.
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ISSN:0028-4793
1533-4406
1533-4406
DOI:10.1056/NEJMoa2314390