Vaccination with leukemia-loaded dendritic cells eradicates residual disease and prevent relapse.
We have previously demonstrated that TNF-alpha gene therapy with myeloid progenitor cells inhibits the progression of 32Dp210 myeloid leukemia in mice. Because TNF-alpha has been shown to induce the activation and maturation of dendritic cells (DCs), we investigated the efficacy of DC-based leukemia vaccine for eradication of residual disease when administered following cytoreductive therapy. Immunization with DC cells loaded with 32Dp210 myeloid leukemia cells (32Dp210 vaccine) was far more effective in preventing the development of leukemia compared to immunization with irradiated leukemia cells alone. The resistance to leukemia could be adoptively transferred to naïve mice with the spleen cells of mice immunized with DC-32Dp210 vaccine, and splenic cells responsible for adoptive transfer of resistance were identified as CD90 + T lymphocytes. Development of immunity in vaccinated mice was associated with the generation of leukemia specific cytotoxic T lymphocytes (CTLs) and secretion of cytokines TNF-alpha and IFN-gamma. Further, immunization with DC-32Dp210 vaccine following cytoreductive therapy with Cytoxan was effective in eradicating residual disease in approximately 50 percent of the animals. However, eradication of residual disease was significantly improved (approximately 74%) when animals were treated with DC-32Dp210 vaccine in which DCs were activated with TNF-alpha prior to loading of 32Dp210 leukemia cells. Cured mice were in molecular remission since Bcr/Abl oncogene could not be amplified from the DNA isolated from the marrow, spleen, or liver of cured mice. Taken together, these data demonstrate the efficacy of DC-based leukemia vaccine for eradication of residual disease and prevention of relapse.
Deeb
Dorrah
D
Department of Surgery, Henry Ford Health System, Detroit, Ml 48202, USA.
Gao
Xiaohua
X
Jiang
Hao
H
Divine
George
G
Dulchavsky
Scott A
SA
Gautam
Subhash C
SC
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000276:immunology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018365:Neoplasm, Residual; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma