Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.

in The New England journal of medicine by Bryan D Choi, Elizabeth R Gerstner, Matthew J Frigault, Mark B Leick, Christopher W Mount, Leonora Balaj, Sarah Nikiforow, Bob S Carter, William T Curry, Kathleen Gallagher, Marcela V Maus

TLDR

  • This study tested a new way to treat a type of brain tumor called glioblastoma. The treatment involved using special cells called CARv3-TEAM-E T cells that were designed to target a specific protein on the tumor. The study found that the treatment was safe and caused the tumor to shrink quickly in all three participants. However, the shrinkage stopped in two of the three participants after a short time. The study suggests that this treatment could be helpful for some people with glioblastoma, but more research is needed to understand how it works and how long it might work for different people.

Abstract

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.).

Overview

  • The study focuses on the use of CARv3-TEAM-E T cells to treat recurrent glioblastoma in three participants. The hypothesis being tested is whether CARv3-TEAM-E T cells can safely and effectively 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).
  • The methodology used for the experiment includes an open-label study design with three participants who received a single intraventricular infusion of CARv3-TEAM-E T cells. The subject demographics were not specified in the abstract. No specific procedures or tests were mentioned in the abstract. The primary objective of the study is to evaluate the safety and efficacy of CARv3-TEAM-E T cells in treating recurrent glioblastoma.

Comparative Analysis & Findings

  • The study compared the outcomes observed under the treatment of CARv3-TEAM-E T cells in three participants with recurrent glioblastoma. The results showed that 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. However, the responses were transient in two of the three participants.

Implications and Future Directions

  • The study's findings suggest that CARv3-TEAM-E T cells are safe and effective in treating recurrent glioblastoma. The study's limitations include the small sample size and the transient nature of the responses in two of the three participants. Future research directions could include expanding the study population, investigating the long-term efficacy of CARv3-TEAM-E T cells, and exploring other combinations of CARs and T-cell-engaging antibodies to improve treatment outcomes.
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