Effect of BCG HSP70 Gene Transfection on Dendritic Cells Derived From Bone Marrow in Children With Acute Leukemia.

Abstract

In this study, immature dendritic cells (imDCs) were transfected with the Bacillé Calmette-Guérin (BCG) heat shock protein 70 (HSP70) gene to investigate the impact on the maturity and function of imDCs from the bone marrow of pediatric patients with acute leukemia. Bone marrow mononuclear cells were isolated from pediatric patients with acute lymphoblastic leukemia who had achieved complete remission at least 6 months prior. The recombinant vector pDisplay-HSP70 was transfected into imDCs. The test groups included 5 subgroups: imDCs (imDCs without special processing), imDC-neos (imDCs transfected with the pDisplay vector), HSP70 (imDCs transfected with the pDisplay-HSP70 vector), tumor necrosis factor α (TNF-α) (imDCs induced with rhTNF-α), and HSP70+TNF-α. Mature dendritic cells (mDCs) from different groups (HSP70, TNF-α, and HSP70+TNF-α) and T cells were cultured. An equal number of lymphocytes and mDCs were used as controls. The proliferation indices of T cells and the cytokine contents (interleukin-12 and interferon-γ) were determined. The HSP70 group and the TNF-α group expressed higher levels of HLA-DR, CD80, and CD86 but lower levels than the HSP70+TNF-α group; there was no significant difference between the HSP70 group and the TNF-α group. The combination of HSP70 and TNF-α induced the highest levels of interleukin-12 and interferon-γ. The outcomes of this study indicated that gene transfection with BCG HSP70 evidently promoted imDC maturity and the antitumor effects of mDC-mediated T cells. It could serve as a candidate gene-modified cell vaccine for tumor immunotherapy.