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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1574-1580. Prepublished online as a Blood First Edition Paper on November 14, 2008; DOI 10.1182/blood-2008-05-155697. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-05-155697v1 113/7/1574    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jenq, R. R. Articles by van den Brink, M. R. M. Search for Related Content PubMed PubMed Citation Articles by Jenq, R. R. Articles by van den Brink, M. R. M. Related Collections Immunobiology Transplantation Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation Robert R. Jenq1,2, Christopher G. King1, Christine Volk1,3, David Suh1, Odette M. Smith1, Uttam K. Rao1, Nury L. Yim1, Amanda M. Holland1, Sydney X. Lu1, Johannes L. Zakrzewski1, Gabrielle L. Goldberg1, Adi Diab1,3, Onder Alpdogan1, Olaf Penack1, Il-Kang Na1, Lucy W. Kappel1, Jedd D. Wolchok13, Alan N. Houghton13, Miguel-Angel Perales13, and Marcel R. M. van den Brink1,2 1 Departments of 1 Immunology and 2 Medicine and 3 Swim Across America Laboratory of Tumor Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8+ T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8+ cells, as well as increased numbers of CD8+ cells producing interferon- (IFN-) and tumor necrosis factor- (TNF-). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell–receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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