Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia
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Open Access
- 26 May 2015
- journal article
- other
- Published by Informa UK Limited in OncoImmunology
- Vol. 4 (11), e1027469
- https://doi.org/10.1080/2162402x.2015.1027469
Abstract
The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2–3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3–4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at www.clinicaltrials.gov as NCT01864889.Keywords
This publication has 62 references indexed in Scilit:
- Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid LeukemiaThe New England Journal of Medicine, 2013
- Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid LeukemiaThe New England Journal of Medicine, 2011
- T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced LeukemiaScience Translational Medicine, 2011
- Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisitedCancer Treatment Reviews, 2010
- Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptorBlood, 2010
- Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in miceJCI Insight, 2010
- Increased Intensity Lymphodepletion Enhances Tumor Treatment Efficacy of Adoptively Transferred Tumor-specific T CellsJournal of Immunotherapy, 2010
- Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primatesJCI Insight, 2008
- Immunological aspects of cancer chemotherapyNature Reviews Immunology, 2008
- Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritisJCI Insight, 2006