PEBL expression did not impair T-cell proliferation, interferon-γ and tumor necrosis factor–α secretion, or cytotoxicity, and eliminated CAR-mediated fratricide. Transduction of anti-CD7 PEBL resulted in virtually instantaneous abrogation of surface CD7 expression in all transduced T cells 2.0% ± 1.7% were CD7 + vs 98.1% ± 1.5% of mock-transduced T cells (n = 5 P <. To downregulate CD7 and control fratricide, we applied a new method (protein expression blocker ), based on an anti-CD7 single-chain variable fragment coupled with an intracellular retention domain. We targeted CD7 with a second-generation CAR (anti-CD7–41BB-CD3ζ), but CAR expression in T lymphocytes caused fratricide due to the presence of CD7 in the T cells themselves. In 49 diagnostic T-ALL samples (including 14 ETP-ALL samples), median CD7 expression was >99% CD7 expression remained high at relapse (n = 14), and during chemotherapy (n = 54). We selected CD7 as a target because of its consistent expression in T-cell acute lymphoblastic leukemia (T-ALL), including the most aggressive subtype, early T-cell precursor (ETP)–ALL. We devised a novel approach based on chimeric antigen receptor (CAR)–redirected T lymphocytes. Effective immunotherapies for T-cell malignancies are lacking.
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