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

树突状细胞(DC)被认为是最有效的抗原提呈细胞，在抗肿瘤免疫中发挥重要作用。在本报告中，我们探讨了利用转导可溶性Flt-1(VEGF-R1)基因的DC进行新的DC治疗的有效性。感染后很少发生细胞毒性反应。通常情况下，血管内皮生长因子由肿瘤细胞分泌，促进肿瘤血管生成。此外，在添加血管内皮生长因子的条件下，骨髓细胞对DC的成熟有抑制作用，从而降低了DC的功能和细胞活力。同时，转染Flt-1基因的DC不受血管内皮生长因子的影响。在肿瘤治疗模型中，转导Flt-1的DCs与LacZ转导的DCs、DCs或未转导的DCs相比，可抑制肿瘤的生长。当腺病毒介导的Flt-1基因转移到DCs中时，感染的DCs释放的分泌型Flt-1捕获了血管内皮生长因子，从而阻断了负信号，使DCs进入成熟状态，产生了强大的抗肿瘤免疫。因此，将Flt-1基因转移到DC中不仅可以发挥抗血管效应，而且可以在VEGFF存在的情况下保存DC的成熟，这一策略可能为癌症患者DC的治疗提供重要的益处。

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.