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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Vydáno v:	The New England journal of medicine Ročník 390; číslo 14; s. 1290 - 1298
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Massachusetts Medical Society 11.04.2024
Edice:	Brief Report
Témata:	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
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0028-4793 1533-4406 1533-4406
DOI:	10.1056/NEJMoa2314390