Immunotherapy for childhood leukemia and solid tumors using dendritic cells

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(1)Generation of leukemia cell-derived dendritic cells (DCs): In order to establish the effective immunotherapy using DCs, DCs were generated directly from leukemia cells. When primary leukemia blasts were cultured in the presence of GM-CSF, TNF- a , Flt-3 ligand, and IL-4, the blasts from the patients with AML M4 and M5a expressed CD 11c, CD80, CD83, CD86. These findings suggested that the leukemia cells of some AML subtypes can differentiate into DCs and might present leukemia-specific antigens directly to T lymphocytes.(2) Expression of cytokine-associated genes in DCs: The expression of cytokine-associated genes in DCs derived from umbilical cord blood (UCB) and adult peripheral blood (APB) was compared. The expression of the Th1 response-related genes and chemokine genes was significantly lower in UCB-DCs than in APB-DC in both maturation states. Calgranulins A and B, which are speculated to induce immune tolerance, showed higher expression in UCB-DCs. The expression of particular genes related to immune responses was significantly different between UCB-and APB-DCs, which may cause functional difference in DC-mediated immunity between newborns and adults.(3)The utility of recombinant Sendai virus(rSeV) for effective DC-mediated immunotherapy against childhood cancer; The ex vivo infection of immature DCs with rSeV induces their spontaneous maturation and activation. We tried to apply this result to the treatment for patients with childhood cancer to setablish a new powerful DC-mediated immunotherapy. Peripheral blood mononuclear cells were isolated from the children with cancer and were cultured in the presence 10% autologous serum, GM-CSF, IL-4 and TNF-α to generate DCs. When the generated DCs were infected with rSeV, the expression of CD80, CD83 and CD86 was markedly enhanced. These findings suggested that rSeV could be a powerful booster for DC-mediated cancer immunotherapy, which might improve the prognosis of children with cancer.