Development of Dendritic Cell-Based Immunotherapy Targeting Tumor Blood Vessels in a Mouse Model of Lung Metastasis
Development of Dendritic Cell-Based Immunotherapy Targeting Tumor Blood Vessels in a Mouse Model of Lung Metastasis
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DOI：
10.1248/bpb.b18-00737
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发表时间：
2019-04-01
影响因子：
2
通讯作者：
Utoguchi, Naoki
中科院分区：
文献类型：
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作者：
Nomura, Tetsuya;Yamakawa, Makie;Utoguchi, Naoki
肿瘤血管为肿瘤组织提供氧气和营养物质，因此认为抑制血管生成会导致肿瘤消退。事实上，癌症和肉瘤等癌症组织中存在正常血管以及异常血管，这让情况变得复杂起来。在这里，我们描述了一种以树突状细胞(DC)为基础的免疫疗法的发展，它针对的是肿瘤内皮细胞(TECs)，而不是正常内皮细胞(ECs)或癌细胞本身。经密度梯度离心后，根据血管紧张素转换酶(ACE)活性阳性，从B16黑色素瘤细胞侵袭的肺组织中分离出富含TEC的部分和富含内皮细胞(EC)的部分。在B16/BL6小鼠黑色素瘤模型中，用从转移肺中分离的TECs裂解物致敏的DC预防性接种显著抑制了肺转移。这表明以肿瘤组织中的TECs为靶点的DC疫苗疗法有望成为治疗远处转移的有效疗法。
Tumor blood vessels supply cancer tissues with oxygen and nutrients, and it was therefore believed that inhibition of angiogenesis would induce tumor regression. In fact, the situation is complicated by the presence of normal blood vessels in cancer tissues such as carcinomas and sarcomas as well as abnormal vessels. Here, we describe the development of a dendritic cell (DC)-based immunotherapy which targets tumor endothelial cells (TECs) rather than normal endothelial cells (ECs) or cancer cells themselves. After density gradient centrifugation, the TEC-rich fraction from lungs invaded by B16 melanoma cells was separated from the endothelial cell (EC)-rich fraction on the basis of positivity for angiotensin-converting enzyme (ACE) activity. Prophylactic vaccination with DCs pulsed with lysates of TECs isolated from lungs with metastases significantly suppressed lung metastasis in this B16/BL6 mouse melanoma model. This suggests that DC-based vaccine therapy targeting TECs in cancers tissue could show promise as an effective therapy for distant metastasis.