Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells

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...

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Bibliographic Details
Published in:Blood 2008-09, Vol.112 (6), p.2261-2271
Main Authors: Till, Brian G., Jensen, Michael C., Wang, Jinjuan, Chen, Eric Y., Wood, Brent L., Greisman, Harvey A., Qian, Xiaojun, James, Scott E., Raubitschek, Andrew, Forman, Stephen J., Gopal, Ajay K., Pagel, John M., Lindgren, Catherine G., Greenberg, Philip D., Riddell, Stanley R., Press, Oliver W.
Format: Article
Language:English
Subjects:
Adult
Aged
Antigens, CD20 - genetics
Clinical Trials and Observations
Female
Humans
Immunotherapy, Adoptive - methods
Lymphocyte Transfusion - methods
Lymphoma, Mantle-Cell - therapy
Lymphoma, Non-Hodgkin - therapy
Male
Middle Aged
Remission Induction
Salvage Therapy - methods
T-Lymphocytes - metabolism
T-Lymphocytes - transplantation
Transfection
Transplantation, Autologous
Treatment Outcome
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Summary: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 showed 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 to 3 weeks in the first 3 patients, who received T cells produced by limiting dilution methods, but persisted 5 to 9 weeks in the next 4 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 show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at www.clinicaltrials.gov as #NCT00012207.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-12-128843