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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Neoplasm / immunology
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Cell Line, Tumor
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Combined Modality Therapy
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Cyclophosphamide / therapeutic use
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Dendritic Cells / immunology
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Doxorubicin / therapeutic use
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Humans
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Immunotherapy, Adoptive / methods*
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / immunology
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Kidney Neoplasms / mortality
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Kidney Neoplasms / secondary
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Kidney Neoplasms / therapy*
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Liver Neoplasms / drug therapy
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Liver Neoplasms / immunology
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Liver Neoplasms / mortality
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Liver Neoplasms / secondary
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Liver Neoplasms / therapy*
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Lung Neoplasms / drug therapy
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Lung Neoplasms / immunology
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Lung Neoplasms / mortality
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Lung Neoplasms / secondary
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Lung Neoplasms / therapy*
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Lymphocyte Activation / immunology
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Lymphoma, Mantle-Cell / drug therapy
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Lymphoma, Mantle-Cell / immunology
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Lymphoma, Mantle-Cell / mortality
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Lymphoma, Mantle-Cell / pathology
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Lymphoma, Mantle-Cell / therapy*
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Mice
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Mice, Inbred NOD
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Neoplasm, Residual
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Prednisone / therapeutic use
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation*
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Treatment Outcome
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Vincristine / therapeutic use
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisone