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The New England Journal of MedicineIntraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

Pioneering Intraventricular CAR T-Cell Therapy Demonstrates Potential in Recurrent Glioblastoma Treatment

In a first-in-human study, CARv3-TEAM-E T cells, targeting both the EGFR variant III and the wild-type EGFR, have been investigated for their therapeutic potential in recurrent glioblastoma. This research offers a glimpse into the efficacy and safety of a novel dual-targeted CAR T-cell therapy, administered intraventricularly, showcasing rapid but transient tumor regression in a majority of participants, without severe adverse effects.

Key Points:

  • CARv3-TEAM-E T cells are engineered to target both the EGFR variant III antigen and the wild-type EGFR protein, offering a new approach to glioblastoma treatment.
  • The study involved three patients with recurrent glioblastoma, demonstrating that the therapy could induce rapid radiographic tumor regression within days after a single intraventricular infusion.
  • No dose-limiting toxic effects or adverse events greater than grade 3 were observed, indicating a favorable safety profile.
  • Two of the three participants showed transient responses, with one participant experiencing a durable response, suggesting variability in treatment efficacy.
  • The treatment targets a heterogeneous disease, aiming to overcome the limitations of single-antigen targeting in solid tumors like glioblastoma.
  • Liquid biopsy results correlated with imaging findings, indicating decreases in EGFRvIII and EGFR copy numbers post-treatment.
  • The study underscores the potential of CAR T-cell therapy in solid tumors, extending beyond its success in hematologic malignancies.
  • Future investigations will focus on enhancing the durability of the response, possibly involving additional infusions or chemotherapy preconditioning.

Every year globally, more than 300,000 cases of glioblastoma are diagnosed, making it the most common primary malignant brain cancer in adults. Despite decades of research, survival for glioblastoma patients remains an average of 15 to 18 months after diagnosis, with just 7% alive after five years.

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