The development of new strategy for "Dendritic cells therapy" in combination with anti-angiogenic therapy for the patients with lung cancer

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Dendritic cells (DCs) are identified as the most effective antigen presenting cells and play an important role in anti-tumor immunity. In this report, we investigate the usefulness of new DCs-therapy, which is utilized DCs transduced with soluble flt-1 (VEGF-R1) gene.DCs were easily transduced soluble flt-1 gene and efficiently secreted Flt-1 protein. And the cytotoxicity was rarely occurred after infection. Generally, VEGF are secreted from tumor cells, and prompt tumor angiogenesis. In addition, under the VEGF-added condition, bone marrow cells were suppressed to maturate DCs, and the function and the cell viability of DCs were reduced as a result of this inhibition. Meanwhile, DCs transfected with flt-1 gene could not be affected by the addition of VEGF. In tumor treatment model, flt-1-transduced DCs suppressed the tumor growth compared to lac Z-transduced DCs, DCs or no treatment.When Adenovirus-mediated gene transfer of "Flt-1" is infected into DCs, VEGF is trapped by secretory form of flt-1 released by infected DCs, so the negative signal is blocked and DCs can become mature state and cause potent anti-tumor immunity. So flt-1 gene transfer into DCs may be very useful for not only antiangionic effect but also preservation of their maturation under the existence of VEGF.This strategy may thus offer significant benefits for DCs-therapy for patients with cancer.