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Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation

By Robert R. Jenq, Christopher G. King, Christine Volk, David Suh, Odette M. Smith, Uttam K. Rao, Nury L. 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

Abstract

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-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). 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

Topics: Transplantation
Publisher: American Society of Hematology
OAI identifier: oai:pubmedcentral.nih.gov:2644085
Provided by: PubMed Central
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