Jiang Tao, Chen Xiao, Zhou Wei, Fan Guoxin, Zhao Peilin, Ren Shengxiang, Zhou Caicun, Zhang Jun
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507 Zheng Min Road, Shanghai, 200433, China.
Department of Anthropotomy and Histo-Embryology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China.
Transl Oncol. 2017 Apr;10(2):132-141. doi: 10.1016/j.tranon.2016.12.002. Epub 2017 Jan 25.
Immunotherapy using dendritic cell (DC) vaccine has the potential to overcome the bottleneck of cancer therapy.
We engineered Lewis lung cancer cells (LLCs) and bone marrow-derived DCs to express tumor-associated antigen (TAA) ovalbumin (OVA) via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo.
The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation (P<.01) and killing of LLCs than control groups (P<.05). Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups (P<.01 and P<.01, respectively). Mechanistically, modified DCs demonstrated enhanced homing to T-cell-rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P<.05), suggesting the potential role on cancer stem-like cells.
These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.
使用树突状细胞（DC）疫苗的免疫疗法有潜力克服癌症治疗的瓶颈。
我们通过编码卵清蛋白（OVA）基因的慢病毒载体质粒，对刘易斯肺癌细胞（LLC）和骨髓来源的DC进行工程改造，使其表达肿瘤相关抗原（TAA）卵清蛋白（OVA）。然后我们在体外和体内测试了修饰后的DC的抗肿瘤作用。
结果表明，体外修饰后的DC与对照组相比，能显著增强T细胞增殖（P<0.01）并增强对LLC的杀伤作用（P<0.05）。此外，与对照组相比，修饰后的DC能减小肿瘤大小并延长荷LLC肿瘤小鼠的生存期（分别为P<0.01和P<0.01）。机制上，修饰后的DC显示出向富含T细胞区域的归巢增强，并触发更多幼稚T细胞分化为细胞毒性T淋巴细胞，这些细胞在肿瘤中表现出显著浸润。有趣的是，修饰后的DC还能显著减少小鼠体内带有干细胞标志物的肿瘤细胞（P<0.05），提示其对癌症干细胞样细胞具有潜在作用。
这些发现表明，用TAA进行生物工程改造的DC可增强抗肿瘤作用，因此代表了一种值得进一步探索的新型抗癌策略。
