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


Authors: Jenq, R. R.; King, C. G.; Volk, C.; Suh, D.; Smith, O. M.; Rao, U. K.; Yim, N. L.; Holland, A. M.; Lu, S. X.; Zakrzewski, J. L.; Goldberg, G. L.; Diab, A.; Alpdogan, O.; Penack, O.; Na, I. K.; Kappel, L. W.; Wolchok, J. D.; Houghton, A. N.; Perales, M. A.; van den Brink, M. R. M.
Article Title: Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation
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 DNAplasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNAvaccination 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<sub>+</sub>. 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<sub>+</sub> cells, as well as increased numbers of CD8 <sub>+</sub> 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. © 2009 by The American Society of Hematoloty.
Keywords: controlled study; survival rate; transplantation, homologous; nonhuman; comparative study; cd8+ t lymphocyte; cd8-positive t-lymphocytes; forkhead transcription factors; animal cell; mouse; phenotype; animals; mice; animal tissue; cell division; melanoma; tumor volume; animal experiment; animal model; allogenic bone marrow transplantation; assay; mice, inbred c57bl; survival time; t lymphocyte receptor; regulatory t lymphocyte; dna; tumor necrosis factor alpha; gamma interferon; cancer vaccines; t-lymphocytes, regulatory; thymus gland; cancer immunization; plasmid; tumor immunity; plasmids; cell fractionation; effector cell; cell count; tumor vaccine; memory cell; bone marrow transplantation; antigens, cd4; vaccines, dna; keratinocyte growth factor; graft recipient; fibroblast growth factor 7; dna immunization; immunologic memory; lymphocyte count; transplantation chimera
Journal Title: Blood
Volume: 113
Issue: 7
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2009-02-12
Start Page: 1574
End Page: 1580
Language: English
DOI: 10.1182/blood-2008-05-155697
PUBMED: 19011222
PROVIDER: scopus
PMCID: PMC2644085
DOI/URL:
Notes: --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    607 Wolchok
  2. Christine Volk
    1 Volk
  3. Olaf Penack
    17 Penack
  4. Il-Kang Na
    24 Na
  5. Adi Diab
    22 Diab
  6. Miguel-Angel Perales
    354 Perales
  7. Robert R Jenq
    100 Jenq
  8. Alan N Houghton
    259 Houghton
  9. Christopher King
    29 King
  10. Sydney X Lu
    48 Lu
  11. Odette Marsinay Smith
    95 Smith
  12. David Suh
    41 Suh
  13. Uttam Keshav Rao
    28 Rao
  14. Nury Yim
    25 Yim
  15. Amanda M Holland
    52 Holland
  16. Lucy Willis
    27 Willis