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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 13, 2008 Accepted November 2, 2008 Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses following murine allogeneic bone marrow transplantation Robert R Jenq, Christopher G King, Christine Volk, David Suh, Odette M Smith, Uttam Rao, Nury Yim, Amanda M. Holland, Sydney X. Lu, Johannes L Zakrzewski, Gabrielle L Goldberg, Adi Diab, Onder Alpdogan, Olaf Penack, Il-Kang Na, Lucy W Kappel, Jedd D Wolchok, Alan N Houghton, Miguel-Angel Perales, and Marcel R.M. van den Brink* Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States Swim Across America Laboratory of Tumor Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States * Corresponding author; email: vandenbm{at}mskcc.org. Keratinocyte growth factor (KGF), 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 prior to 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 to controls, generate increased numbers of tumor-specific CD8+ cells, as well as increased numbers of CD8+ cells producing IFN- and TNF-. We also found unanticipated benefits to anti-tumor immunity with KGF administration. KGF-treated allo-BMT recipients have an improved T effector-to-regulatory T cell ratio, 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 KGF can function as a potent vaccine adjuvant following allo-BMT through its effects on post-transplant T cell reconstitution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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