PMID- 15824323 OWN - NLM STAT- MEDLINE DCOM- 20050801 LR - 20181113 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 102 IP - 18 DP - 2005 May 3 TI - Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells. PG - 6461-6 AB - 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. FAU - Groh, Veronika AU - Groh V AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. vgroh@fhcrc.org FAU - Li, Yongqing Q AU - Li YQ FAU - Cioca, Daniel AU - Cioca D FAU - Hunder, Naomi N AU - Hunder NN FAU - Wang, Wei AU - Wang W FAU - Riddell, Stanley R AU - Riddell SR FAU - Yee, Cassian AU - Yee C FAU - Spies, Thomas AU - Spies T LA - eng GR - R37 AI030581/AI/NIAID NIH HHS/United States GR - R01 AI052319/AI/NIAID NIH HHS/United States GR - AI30581/AI/NIAID NIH HHS/United States GR - AI52319/AI/NIAID NIH HHS/United States GR - R01 AI030581/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050411 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, Neoplasm) RN - 0 (DNA Primers) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (MHC class I-related chain A) RN - 82115-62-6 (Interferon-gamma) SB - IM CIN - Proc Natl Acad Sci U S A. 2005 May 3;102(18):6243-4. PMID: 15851655 MH - Antibodies, Monoclonal/immunology/therapeutic use MH - Antigens, Neoplasm/*immunology MH - Cell Line, Tumor MH - Cross-Priming/*immunology MH - Cytotoxicity Tests, Immunologic MH - DNA Primers MH - Dendritic Cells/*immunology MH - Flow Cytometry MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Immunity, Cellular/*immunology MH - Immunization, Passive/*methods MH - Interferon-gamma/metabolism MH - Neoplasms/immunology/*therapy MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/immunology PMC - PMC1088382 EDAT- 2005/04/13 09:00 MHDA- 2005/08/02 09:00 PMCR- 2005/11/03 CRDT- 2005/04/13 09:00 PHST- 2005/04/13 09:00 [pubmed] PHST- 2005/08/02 09:00 [medline] PHST- 2005/04/13 09:00 [entrez] PHST- 2005/11/03 00:00 [pmc-release] AID - 0501953102 [pii] AID - 01026461 [pii] AID - 10.1073/pnas.0501953102 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2005 May 3;102(18):6461-6. doi: 10.1073/pnas.0501953102. Epub 2005 Apr 11.