Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

Choi, Bryan D. M.D., Ph.D.
Gerstner, Elizabeth R. M.D.
Frigault, Matthew J. M.D.
Leick, Mark B. M.D.
Mount, Christopher W. M.D., Ph.D.
Balaj, Leonora Ph.D.
Nikiforow, Sarah M.D., Ph.D.
Carter, Bob S. M.D., Ph.D.
Curry, William T. M.D.
Gallagher, Kathleen Ph.D.
Maus, Marcela V. M.D., Ph.D.

From the Cellular Immunotherapy Program (B.D.C., M.J.F., M.B.L., C.W.M., K.G., M.V.M.) and Krantz Family Center for Cancer Research (M.B.L., K.G., M.V.M.), Mass General Cancer Center, and the Departments of Neurology (E.R.G.), Pathology (C.W.M., K.G.), Neurosurgery (B.D.C., L.B., B.S.C., W.T.C.), and Medicine (M.J.F., M.B.L., M.V.M.), Massachusetts General Hospital and Harvard Medical School, and Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber/Harvard Cancer Center (S.N.) — both in Boston.

Dr. Maus can be contacted at [email protected]. Any other requests related to this trial can be addressed to [email protected].

This article was published on March 13, 2024, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by a grant (to Dr. Maus) from Gateway for Cancer Research; grants from the Mass General Cancer Center and Mass General Brigham; the National Gene Vector Biorepository at Indiana University, which is funded under National Cancer Institute contract HSN261201500003I Task Order No. HHSN26100077; and philanthropic gifts (directed to the Cellular Immunotherapy Program).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 390(14):p 1290-1298, April 11, 2024. | DOI: 10.1056/NEJMoa2314390

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.)