Intraventricular CARv3-TEAM-E T-Cell Therapy for Recurrent Glioblastoma
abstract
This abstract is available on the publisher's site.
Access this abstract nowIn 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.)
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Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma
N. Engl. J. Med 2024 Mar 13;[EPub Ahead of Print], BD Choi, ER Gerstner, MJ Frigault, MB Leick, CW Mount, L Balaj, S Nikiforow, BS Carter, WT Curry, K Gallagher, MV MausFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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CAR technology has revolutionized the treatment of hematological malignancies and is showing promise for solid tumors. In our manuscript, we describe our clinical experience with a modified form of CAR T cells called CARv3-TEAM-E in patients with glioblastoma, the most common and most aggressive form of primary brain cancer, which remains fatal despite currently available therapy.
CARv3-TEAM-E consists of a two-in-one engineered T cell: it contains a CAR that targets an oncogenic variant of the EGFR (variant III), and it serves as both a factory and delivery vehicle as it secretes a second bioactive agent, namely a T-cell–engaging antibody molecule (TEAM) against the more broadly expressed wild-type EGFR receptor at the tumor site. Using this approach, even unmodified T cells in a patient’s tumor or circulation can be sensitized against the tumor and converted into cytotoxic killers.
Our first 3 patients treated with CARv3-TEAM-E were observed to have rapid and early regression of even bulky, invasive glioblastomas involving the parenchyma of the brain. The therapy was safe without dose-limiting toxicity. Future studies will be focused on understanding and enhancing the durability of responses to this approach and investigating the ways in which the CAR-TEAM platform might be applicable to other cancers.