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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2261-2271.
Prepublished online as a Blood First Edition Paper on May 28, 2008; DOI 10.1182/blood-2007-12-128843.
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Submitted December 17, 2007
Accepted May 3, 2008
Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells
Brian G Till*, Michael C Jensen, Jinjuan Wang, Eric Y Chen, Brent L Wood, Harvey A Greisman, Xiaojun Qian, Scott E James, Andrew Raubitschek, Stephen J Forman, Ajay K Gopal, John M Pagel, Catherine G Lindgren, Philip D Greenberg, Stanley R Riddell, and Oliver W. Press
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle
Pediatric Hematology-Oncology, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA
Department of Laboratory Medicine, University of Washington, Seattle
Department of Radioimmunotherapy, City of Hope National Medical Center, Duarte, CA
Department of Hematology and BMT, City of Hope National Medical Center, Duarte, CA
Department of Medicine, University of Washington, Seattle
* Corresponding author; email: tillb{at}fhcrc.org.
Adoptive immunotherapy with T cells expressing a tumor-specific chimeric T cell receptor is a promising approach to cancer therapy that has not previously been explored for the treatment of lymphoma in human subjects. We report the results of a proof-of-concept clinical trial in which patients with relapsed or refractory indolent B-cell lymphoma or mantle cell lymphoma were treated with autologous T cells genetically modified by electroporation with a vector plasmid encoding a CD20-specific chimeric T cell receptor and neomycin resistance gene. Transfected cells were immunophenotypically similar to CD8+ effector cells and demonstrated CD20-specific cytotoxicity in vitro. Seven patients received a total of 20 T cell infusions, with minimal toxicities. Modified T cells persisted in vivo 1-3 weeks in the first three patients, who received T cells produced by limiting dilution methods, but persisted 5-9 weeks in the next four patients who received T cells produced in bulk cultures followed by 14 days of low-dose subcutaneous interleukin-2 (IL-2) injections. Of the 7 treated patients, 2 maintained a previous complete response, 1 achieved a partial response, and 4 had stable disease. These results demonstrate the safety, feasibility, and potential anti-tumor activity of adoptive T cell therapy using this approach. This study is registered at http://clinicaltrials.gov as NCT00012207.
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