Induction of immunity to neuroblastoma early after syngeneic hematopoietic stem cell transplantation using a novel mouse tumor vaccine.
Autologous HSCT has resulted in improved event-free survival in patients with advanced neuroblastoma, but most of these patients still relapse. We previously reported that transient transfection of mouse neuroblastoma cells with plasmid DNA vectors encoding immune costimulatory molecules generates cell-based vaccines capable of inducing potent antitumor T cell immunity. In this study, we explored the effectiveness of tumor vaccine administration soon after HSCT. Soon after transplantation, only vaccinated mice that had received an adoptive transfer of syngeneic T cells survived tumor challenge. Tumor protective immunity in the transplant recipients was dependent on CD4(+) and CD8(+) T cells, and tumor-reactive T cells in the spleens of vaccinated mice could be detected in IFN-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. Our data indicate that the adoptive transfer of T cells was absolutely required for induction of protective immunity by the tumor vaccine. Adoptive transfer of T cells accelerated T cell reconstitution, but it also resulted in increased percentages of CD4(+)CD25(+)Foxp3(+) cells soon after HSCT. Treatment of HSC transplant recipients with an anti-CD25 mAb before tumor vaccination inhibited antitumor immunity and significantly decreased the number of IFN-gamma-secreting tumor-specific CD4 T cells. However, physical depletion of CD25(+) cells from the adoptively transferred splenocytes appeared to increase the efficacy of tumor vaccination. Collectively, these results demonstrate that anti-neuroblastoma immunity can be induced soon after HSCT using a novel cell-based cancer vaccine. However, sufficient numbers of T cells must be added to the graft to achieve protective antitumor immunity, and depletion of CD25(+) T cells from adoptively transferred T cells might provide some additional benefit. These translational studies will aid in our development of post-HSCT vaccines for neuroblastoma.
Jing
Weiqing
W
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Orentas
Rimas J
RJ
Johnson
Bryon D
BD
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D007109:Immunity; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D009447:Neuroblastoma / Q000276:immunology* / Q000628:therapy; D015996:Survival Rate; D013601:T-Lymphocytes / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014185:Transplantation, Isogeneic
D019496:Cancer Vaccines