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

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Item Type:	Article
Title:	Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation
Creators Name:	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. and van den Brink, M.R.M.
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-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). 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.
Keywords:	Bone Marrow Transplantation, Cancer Vaccines, CD4Antigens, CD8-Positive T-Lymphocytes, Cell Division, DNA Vaccines, Fibroblast Growth Factor 7, Forkhead Transcription Factors, Homologous Transplantation, Immunologic Memory, Lymphocyte Count, Plasmids, Regulatory T-Lymphocytes, Survival Rate, Thymus Gland, Transplantation Chimera, Animals, Mice
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	113
Number:	7
Page Range:	1574-1580
Date:	12 February 2009
Official Publication:	https://doi.org/10.1182/blood-2008-05-155697
PubMed:	View item in PubMed

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