Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia

作者：Stephan A. Grupp, Michael D. Kalos, David Maxwell Barrett, Richard Aplenc, David L. Porter, Susan R. Rheingold, David T. Teachey, Anne Chew, Bernd Hauck, John Fraser Wright, Michael C. Milone, Bruce L. Levine, Carl H. June · 发表于：New England Journal of Medicine · 年份：2013 · DOI：10.1056/nejmoa1215134 · 被引用次数：3530 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research

Chimeric antigen receptor-modified T cells with specificity for CD19 have shown promise in the treatment of chronic lymphocytic leukemia (CLL). It remains to be established whether chimeric antigen receptor T cells have clinical activity in acute lymphoblastic leukemia (ALL). Two children with relapsed and refractory pre-B-cell ALL received infusions of T cells transduced with anti-CD19 antibody and a T-cell signaling molecule (CTL019 chimeric antigen receptor T cells), at a dose of 1.4×10(6) to 1.2×10(7) CTL019 cells per kilogram of body weight. In both patients, CTL019 T cells expanded to a level that was more than 1000 times as high as the initial engraftment level, and the cells were identified in bone marrow. In addition, the chimeric antigen receptor T cells were observed in the cerebrospinal fluid (CSF), where they persisted at high levels for at least 6 months. Eight grade 3 or 4 adverse events were noted. The cytokine-release syndrome and B-cell aplasia developed in both patients. In one child, the cytokine-release syndrome was severe; cytokine blockade with etanercept and tocilizumab was effective in reversing the syndrome and did not prevent expansion of chimeric antigen receptor T cells or reduce antileukemic efficacy. Complete remission was observed in both patients and is ongoing in one patient at 11 months after treatment. The other patient had a relapse, with blast cells that no longer expressed CD19, approximately 2 months after treatment. Chimeric antigen re...