title: DNA immunization against tissue-restricted antigens enhances tumor immunity after allogeneic hemopoietic stem cell transplantation.
abstract: Malignant relapse remains a major problem for recipients of allogeneic hemopoietic stem cell transplantation (HSCT). We hypothesized that immunization of allogeneic HSCT recipients against tissue-restricted Ags using DNA vaccines would decrease the risk of relapse without enhancing graft-vs-host disease (GVHD). Using the mouse B16 melanoma model, we found that post-HSCT DNA immunization against a single tumor Ag induces tumor rejection that is significantly greater than HSCT alone in a T cell-depleted MHC-matched minor Ag-mismatched allogeneic HSCT model (LP --> B6). In treatment models, post-HSCT DNA immunization provides significantly greater overall survival than the vaccine alone. Donor leukocyte infusion further enhances tumor-free survival, including in treatment models. There was no GVHD in HSCT recipients treated with DNA vaccination and donor leukocyte infusion. Further analysis demonstrated that these effects are dependent on CD8+ T cells of donor origin that recognize multiple epitopes. These results demonstrate that DNA immunization against tissue-restricted Ags after allogeneic T cell-depleted HSCT can induce potent antitumor effects without causing GVHD.
authors.affiliation: Swim Across America Laboratory of Tumor Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. peralesm@mskcc.org
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.forename: Adi
authors.initials: A
authors.lastname: Diab
authors.forename: Adam D
authors.initials: AD
authors.lastname: Cohen
authors.forename: Deonka W
authors.initials: DW
authors.lastname: Huggins
authors.forename: José A
authors.initials: JA
authors.lastname: Guevara-Patiño
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hubbard
authors.forename: Manuel E
authors.initials: ME
authors.lastname: Engelhorn
authors.forename: Adam A
authors.initials: AA
authors.lastname: Kochman
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Eng
authors.forename: Fariborz
authors.initials: F
authors.lastname: Mortazavi
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.forename: Theis H
authors.initials: TH
authors.lastname: Terwey
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D017708:Leukocyte Transfusion; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019444:Vaccines, DNA