title: Imatinib mesylate effectively combines with chaperone-rich cell lysate-loaded dendritic cells to treat bcr-abl+ murine leukemia.
abstract: Imatinib mesylate has become an effective agent for the treatment of chronic myeloid leukemia (CML). However, the development of drug resistance has led to examination of combination therapies. In this study, we investigated the effects of combining imatinib with immunotherapy against a murine bcr-abl(+) leukemia, 12B1. We have previously shown that multiple chaperone proteins may be enriched into a vaccine form from tumor cell lysates by a free-solution isoelectric focusing method. We refer to these vaccines as chaperone-rich cell lysates (CRCLs) and have found that they are potent immunologic agents against a variety of murine tumors, including 12B1. We now demonstrate that the combination of imatinib with dendritic cells loaded with 12B1-derived CRCL yields high activation of anti-12B1-specific T cells and potent antitumor activity, resulting in tumor-free survival in up to 63% of mice with bcr-abl(+) 12B1 tumors. Our data suggest that immunotherapy can be effectively combined with imatinib for the treatment of CML.
authors.affiliation: Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D000068877:Imatinib Mesylate; D007371:Interferon-gamma / Q000096:biosynthesis; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000502:physiology*; D010766:Phosphorylation; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D019496:Cancer Vaccines; D018832:Molecular Chaperones; D010879:Piperazines; D011743:Pyrimidines; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl