Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy
Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy
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DOI：
10.1158/1535-7163.mct-08-0277
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发表时间：
2008-07-01
影响因子：
5.7
通讯作者：
Chung, June-Key
中科院分区：
文献类型：
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作者：
Jeon, Yong Hyun;Choi, Yun;Chung, June-Key
我们研究了组合 hMUC1 疫苗接种和 hNIS 放射性碘基因治疗的优点，并评估了其在动物肿瘤模型中的杀肿瘤作用。将 CMNF（表达 hMUC1、hNIS 和萤火虫荧光素酶的 CT26）细胞移植到 28 只小鼠中，在肿瘤攻击后 4 和 11 天，对荷瘤小鼠进行肌内免疫。使用 pcDNA3.1 或 pcDNA-hMUC1 疫苗，随后腹腔注射 PBS 或 I-131。 [四组（每组7只小鼠）：pcDNA3.1 + PBS、phMUC1 + PBS、pcDNA3.1 + I-131和phMUC1 + I-131组]。肿瘤攻击后三十二天，我们用 CMNF 细胞重新攻击 pcDNA3.1 + I-131 和 phMIUC11 + I-131 组的小鼠。通过生物发光监测肿瘤进展和无肿瘤小鼠（%）。我们研究了联合疗法产生的 hMUC1 相关免疫反应。通过肿瘤攻击后32天的生物发光，在phMUC1+131组中观察到显着的肿瘤生长抑制。 phMUC1 + I-131组中的小鼠在肿瘤再攻击后表现出完全表达hMUC1的肿瘤抑制，而pcDNA3.1 + I-131组中的小鼠则没有。 phMUC1 + I-131 组的无瘤小鼠 (%) 远高于其他三组。 phMUC1 + I-131 组中 hMUC1 相关 CD8(+)IFN(-gamma)(+) T 细胞水平高于其他三组。 phMUC1+I-131组中负载hMUC1的CD11(+)细胞被发现在产生hMUC1相关CD8(+)IFN-γ(+)T细胞方面最有效。 phMUC1 + I-131组中hMUC1相关细胞毒性T细胞的活性高于其他三组。我们的数据表明，phMUC1 + I-131 联合疗法可协同产生针对已确定的表达 hMUC1 的癌症的显着杀肿瘤作用。
We examined the merits of combinatorial hMUC1 vaccination and hNIS radioiodine gene therapy and evaluated its tumoricidal effects in an animal tumor model. CMNF (CT26 expressing hMUC1, hNIS, and firefly luciferase) cells were transplanted into 28 mice, and 4 and 11 days after tumor challenge, tumor-bearing mice were immunized i.m. with pcDNA3.1 or pcDNA-hMUC1 vaccine and subsequently administered PBS or I-131 i.p. [four groups (7 mice per group): pcDNA3.1 + PBS, phMUC1 + PBS, pcDNA3.1 + I-131, and phMUC1 + I-131 groups]. Thirtytwo days after tumor challenge, we rechallenged mice in the pcDNA3.1 + I-131 and phMIUC11 + I-131 groups with CMNF cells. Tumor progression and tumor-free mice (%) were monitored by bioluminescence. We investigated hMUC1-associated immune response generated by combination therapy. Marked tumor growth inhibition was observed in the phMUC1 + 131, group by bioluminescence at 32 days after tumor challenge. Mice in phMUC1 + I-131 group showed complete hMUC1 -expressing tumor suppression after tumor rechallenge, whereas mice in the pcDNA3.1 + I-131 group did not. The tumor-free mice (%) were much higher in the phMUC1 + I-131 group than in the other three groups. Levels of hMUC1 -associated CD8(+)IFN(-gamma)(+) T cells were higher in the phMUC1 + I-131 group than in the other three groups. hMUC1-loaded CD11(+) cells in the phMUC1 + I-131 group were found to be most effective at generating hMUC1-associated CD8(+)IFN-y(+) T cells. The activities of hMUC1-associated cytotoxic T cells in the phMUC1 + I-131 group were higher than in the other three groups. Our data suggest that phMUC1 + I-131 combination therapy synergistically generates marked tumoricidal effects against established hMUC1-expressing cancers.