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Vaccination with leukemia-loaded dendritic cells eradicates residual disease and prevent relapse
Dorrah Deeb, Xiaohua Gao, Hao Jiang, George Divine, Scott A. Dulchavsky and Subhash C. Gautam

We have previously demonstrated that TNF-a gene therapy with myeloid progenitor cells inhibits the progression of 32Dp210 myeloid leukemia in mice. Because TNF-a 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-a and IFN-g. Further, immunization with DC-32Dp210 vaccine following cytoreductive therapy with Cytoxan was effective in eradicating residual disease in ~50 percent of the animals. However, eradication of residual disease was significantly improved (~74%) when animals were treated with DC-32Dp210 vaccine in which DCs were activated with TNF-a 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.

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