title: Optimized adoptive T-cell therapy for the treatment of residual mantle cell lymphoma.
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.
authors.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.
authors.forename: Corey M
authors.initials: CM
authors.lastname: Munger
authors.forename: Ganapati V
authors.initials: GV
authors.lastname: Hegde
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Shantaram S
authors.initials: SS
authors.lastname: Joshi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D018365:Neoplasm, Residual; D011241:Prednisone / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone