Targeted Hsp70 expression combined with CIK-activated immune reconstruction synergistically exerts antitumor efficacy in patient-derived hepatocellular carcinoma xenograft mouse models.
Targeted Hsp70 expression combined with CIK-activated immune reconstruction synergistically exerts antitumor efficacy in patient-derived hepatocellular carcinoma xenograft mouse models.
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靶向 Hsp70 表达结合 CIK 激活的免疫重建在患者来源的肝细胞癌异种移植小鼠模型中协同发挥抗肿瘤功效
DOI：
10.18632/oncotarget.2835
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发表时间：
2015-01-20
期刊：
影响因子：
--
通讯作者：
Su C
中科院分区：
文献类型：
--
作者：
Hu H;Qiu Y;Guo M;Huang Y;Fang L;Peng Z;Ji W;Xu Y;Shen S;Yan Y;Huang X;Zheng J;Su C
患者源性肿瘤异种移植（patient-derived tumor xenograft， PDTX）模型能够在患者体内再现与肿瘤细胞相似的自然遗传背景和相似的生物学行为，有利于评估癌症的个性化治疗。为了验证Survivin启动子调控的表达Hsp70的溶瘤腺病毒治疗策略的靶向性和有效性，本研究在裸鼠身上建立了肝细胞癌（HCC）的PDTX模型，并将细胞因子诱导的杀伤细胞（CIK）静脉注入小鼠体内，部分重建小鼠免疫功能。结果表明，无论是CIK细胞输注引起的免疫抗肿瘤作用，还是溶瘤腺病毒复制产生的溶瘤作用都是非常有限的。而表达Hsp70的溶瘤腺病毒与CIK细胞联合治疗后，协同抑瘤效果明显增强。溶瘤腺病毒介导Hsp70在癌组织中的特异性表达，使CIK趋化，诱导CD3+ T细胞浸润肿瘤基质，从而表现出抗肿瘤活性。Survivin高表达的高度恶性肿瘤异种移植物抗肿瘤效果更明显。该策略可协同激活多种抗肿瘤机制，发挥有效的抗肿瘤活性，对肝癌异种移植物生长有显著抑制作用。
The patient-derived tumor xenograft (PDTX) models can reproduce a similar natural genetic background and similar biological behaviors to tumor cells in patients, which is conducive to the assessment of personalized cancer treatment. In this study, to verify the targeting and effectiveness of the therapeutic strategy using a Survivin promoter-regulated oncolytic adenovirus expressing Hsp70, the PDTX models of hepatocellular carcinoma (HCC) were established in nude mice and the cytokine-induced killer (CIK) cells were intravenously infused into mice to partially reconstruct the mouse immune function. The results demonstrated that, either the immune anti-tumor effect caused by CIK cell infusion or the oncolytic effect generated by oncolytic adenovirus replication was very limited. However, the synergistic tumor inhibitory effect was significantly enhanced after treatments with oncolytic adenovirus expressing Hsp70 combined with CIK cells. Oncolytic adenovirus mediated the specific expression of Hsp70 in cancer tissues allowed the CIK chemotaxis, and induce the infiltration of CD3+ T cells in tumor stroma, thereby exhibiting anti-tumor activity. The anti-tumor effect was more effective for the highly malignant tumor xenografts with highly Survivin expression. This strategy can synergistically activate multiple anti-tumor mechanisms and exert effective anti-tumor activities that have a significant inhibitory effect against the growth of HCC xenografts.
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影响因子：
6.2
作者：
Stebbing, Justin;Paz, Keren;Schwartz, Gary K.;Wexler, Leonard H.;Maki, Robert;Pollock, Raphael E.;Morris, Ronnie;Cohen, Richard;Shankar, Arjun;Blackman, Glen;Harding, Victoria;Vasquez, David;Krell, Jonathan;Ciznadija, Daniel;Katz, Amanda;Sidransky, David
通讯作者：
Sidransky, David
影响因子：
9.7
作者：
Malaney, Prerna;Nicosia, Santo V.;Dave, Vrushank
通讯作者：
Dave, Vrushank
影响因子：
3.7
作者：
Böttger E;Multhoff G;Kun JF;Esen M
通讯作者：
Esen M
影响因子：
2.2
作者：
Cho, Yong Beom;Hong, Hye Kyung;Lee, Woo Yong
通讯作者：
Lee, Woo Yong
OCT4增加BIRC5和CCND1表达并促进肝细胞癌的癌症进展
影响因子：
3.8
作者：
Cao L;Li C;Shen S;Yan Y;Ji W;Wang J;Qian H;Jiang X;Li Z;Wu M;Zhang Y;Su C
通讯作者：
Su C