title: Ineffective vaccination against solid tumors can be enhanced by hematopoietic cell transplantation.
abstract: Vaccination with tumor Ags has not been an effective treatment for solid tumors. The goal of the current study was to determine whether a combination of vaccination and hematopoietic cell transplantation (HCT) can effectively treat primary, disseminated, or metastatic CT26 and MC38 murine colon tumors. Vaccination of tumor-bearing mice with irradiated tumor cells and CpG adjuvant failed to alter progressive tumor growth. However, mice bearing primary, disseminated lung, or metastatic liver tumors were uniformly cured after administration of total body irradiation, followed by the transplantation of hematopoietic progenitor cells and T cells from syngeneic, but not allogeneic vaccinated donors. Requirements for effective treatment of tumors included irradiation of hosts, vaccination of donors with both tumor cells and CpG, transfer of both CD4(+) and CD8(+) T cells along with progenitor cells, and ability of donor cells to produce IFN-gamma. Irradiation markedly increased the infiltration of donor T cells into the tumors, and the combined irradiation and HCT altered the balance of tumor-infiltrating cells to favor CD8(+) effector memory T cells as compared with CD4(+)CD25(+)FoxP3(+) T regulatory cells. The combination of vaccination and autologous hematopoietic cell transplantation was also effective in treating tumors. In conclusion, these findings show that otherwise ineffective vaccination to solid nonhematologic tumors can be dramatically enhanced by HCT.
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Filatenkov
authors.forename: Antonia M S
authors.initials: AM
authors.lastname: Müller
authors.forename: William Wei-Lin
authors.initials: WW
authors.lastname: Tseng
authors.forename: Sussan
authors.initials: S
authors.lastname: Dejbakhsh-Jones
authors.forename: Daniel
authors.initials: D
authors.lastname: Winer
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.forename: Samuel
authors.initials: S
authors.lastname: Strober
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation; D014611:Vaccination / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines