title: Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells.
abstract: Dendritic cells (DCs) have the capacity to prime tumor-specific T cell responses and are considered as potentially effective vaccines for immunotherapy of cancer. Critical parameters in the development of DC vaccines are the source of tumor antigen (TA) and the mode of DC-loading. Whole tumor cells contain complex assortments of TA, which has been exploited to enhance cross-presentation to CD8 T cells by DCs loaded with anti-syndecan mAb-opsonized myeloma cells. This approach may be broadly improved by targeting the MHC class I chain-related protein A (MICA), which is frequently and abundantly expressed on most if not all types of epithelial cancers but not in normal tissues except intestinal mucosa. Loading of DC with anti-MICA mAb-coated breast, melanoma, or ovarian tumor lines or uncultured ovarian cancer cells efficiently promoted TA cross-presentation and priming of multivalent anti-tumor CD8 and CD4 T cell responses. These were of substantially greater breadth and magnitude than those of T cells primed by peptide-pulsed or apoptotic tumor cell-loaded DCs. These results may advance DC vaccine development and provide a platform for adoptive T cell therapy and TA discovery. These results further suggest that antibody targeting of MICA might be applicable to elicit T cell immunity against tumors of diverse tissue origins in cancer patients.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. vgroh@fhcrc.org
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.forename: Yongqing Q
authors.initials: YQ
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Cioca
authors.forename: Naomi N
authors.initials: NN
authors.lastname: Hunder
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Cassian
authors.initials: C
authors.lastname: Yee
authors.forename: Thomas
authors.initials: T
authors.lastname: Spies
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007116:Immunization, Passive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D007371:Interferon-gamma