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Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1857-1864 IMMUNOBIOLOGY Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4+ and CD8+ T lymphocyte responses Wolfgang Herr, Elena Ranieri, Walter Olson, Hassane Zarour, Loreto Gesualdo, and Walter J. Storkus From the Department of Surgery and Department of Molecular Genetics and Biochemistry, University of Pittsburgh Medical Center, Pittsburgh, PA. Immunotherapy trials targeting the induction of tumor-reactive T-cell responses in cancer patients appear to hold significant promise. Because nonmutated lineage-specific antigens and mutated idiotypic antigens may be coexpressed by tumor cells, the use of autologous tumor material to promote the broadest range of antitumor T-cell specificities has significant clinical potential in cancer vaccination trials. As a model for vaccination in the cancer setting, we chose to analyze the promotion of T-cell responses against Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell line (B-LCL)-derived antigens in vitro. A series of bulk antigenic formats (freeze-thaw lysate, trifluoroacetic acid lysate, extracted membranes, affinity-purified MHC class I- and class II-presented peptides, acid-eluted peptides) prepared from EBV B-LCLs were tested for their ability to stimulate EBV B-LCL-reactive CD4+ and CD8+ T lymphocytes in vitro when pulsed onto autologous dendritic cells (DCs). DC presentation of freeze-thaw lysate material derived from (either autologous or allogeneic) EBV B-LCLs with an Mr of 10 kd or larger stimulated optimal anti-EBV B-LCL responsiveness from freshly isolated CD4+ and CD8+ peripheral blood T cells. These in vivo "memory" T-cell responses were observed only in EBV-seropositive donors. CD4+ T-cell responses to lysate-pulsed DCs were Th1 type (ie, strong interferon- and weak interleukin-5 responses). While CD8+ T-cell responses were also observed in interferon- Elispot assays and in cytotoxicity assays, these responses were of low frequency unless the DC stimulators were induced to "mature" after being fed with tumor lysates. Optimal-length, naturally processed, and MHC class I- or class II-presented tumor peptides were comparatively poorly immunogenic in this model system. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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