Optimized adoptive T-cell therapy for the treatment of residual mantle cell lymphoma |
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Authors: | Corey M. Munger Ganapati V. Hegde Dennis D. Weisenburger Julie M. Vose Shantaram S. Joshi |
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Affiliation: | Department of Genetics, Cell Biology and Anatomy, Center for Research in Leukemia and Lymphoma, University of Nebraska Medical Center, Omaha, NE, 68198-6395, USA. |
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Abstract: | Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm with few patients achieving long-term survival with current treatment regimens. High-dose therapy is effective in reducing the tumor burden; however, patients eventually relapse due to minimal residual disease. Having demonstrated efficacy in other malignancies, the effectiveness of dendritic cell-based immunotherapy for minimal residual MCL was examined. We demonstrated that dendritic cells (DC) primed with MCL antigens stimulated the activation of MCL-specific T cells that recognized and destroyed both MCL cell lines and primary MCL in vitro. In addition, in vivo studies demonstrated that adoptively transferred MCL-specific T cells were able to significantly inhibit tumor growth in mice with minimal residual MCL. Subsequently, when combined with CHOP chemotherapy, adoptive T-cell therapy was able to significantly extend the survival of the mice by further reducing the tumor burden. These results clearly show that MCL-specific cellular immunotherapy is effective in treating minimal residual MCL, paving the way for future clinical studies. |
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