Jiang Nan, Wang Gen-Shu, Li Hua, Zhang Jian, Zhang Jun-Feng, Yi Shu-Hong, Yi Hui-Min, Yang Yang, Cai Chang-Jie, Lu Min-Qiang, Chen Gui-Hua
Department of Liver Transplant Center, Third Affiliated Hospital of Sun Yat-sen University, Transplantation Research Institute of Sun Yat-sen University, Guangzhou 510630, China.
Zhonghua Zhong Liu Za Zhi. 2009 Jun;31(6):405-9.
To investigate the effects of dendritic cells (DCs) infected with adenovirus vector encoding mTERT on induction of mTERT antigen specific immunity against H22 hepatoma in vivo.
Forty Bal B/c mice were subcutaneously immunized with Ad-mTERT infected DC. Cytotoxicity of mTERT specific CTL was determined by 51Cr release assay. IL-2 and IFN-gamma were tested by ELISA. IFN-gamma ELISPOT assays were performed for measuring antigen specific IFN-gamma production by T cells. Tumor size and survival of the immunized mice were recorded and evaluated whether preexisting hepatoma metastases could be supressed after immunization with mTERT-expressing DCs.
The lytic activity of CTL, IL-2 (871.25 pg/ml), IFN-gamma (169.15 ng/ml) and IFN-gamma secreting cells (378/10(6) spleen cells) elicited by the Ad-mTERT infected DCs were much stronger and higher than that by Ad-GFP group (131.6 pg/ml, 15.4 ng/ml, 36/10(6) spleen cells, P<0.05), DC group (71.3 pg/ml, 10.5 ng/ml, 21/10(6) spleen cells, P<0.05), PBS group (65.8 pg/ml, 7.4 ng/ml, 18/10(6) spleen cells, P<0.05). In prophylaxis and treatment experiment the Ad-mTERT/DCs immunized mice lived significantly longer than other groups, demonstrating that primary DCs were genetically modified to express the mTERT antigen and could suppress the tumor growth.
Adenovirus vector mediated mTERT infected DCs can effectively induce mTERT antigen specific antitumor activity, and can induce protective and therapeutic antitumor immunity.
研究感染编码人端粒酶逆转录酶(mTERT)腺病毒载体的树突状细胞(DCs)在体内对H22肝癌诱导mTERT抗原特异性免疫的影响。
40只Bal B/c小鼠皮下注射Ad-mTERT感染的DC进行免疫。采用51Cr释放试验测定mTERT特异性CTL的细胞毒性。通过ELISA检测白细胞介素-2(IL-2)和干扰素-γ(IFN-γ)。进行IFN-γ ELISPOT试验以测量T细胞产生的抗原特异性IFN-γ。记录免疫小鼠的肿瘤大小和生存情况,并评估用表达mTERT的DC免疫后是否可以抑制预先存在的肝癌转移。
Ad-mTERT感染的DCs诱导的CTL裂解活性、IL-2(871.25 pg/ml)、IFN-γ(169.15 ng/ml)和IFN-γ分泌细胞(378/10(6)脾细胞)比Ad-GFP组(131.6 pg/ml、15.4 ng/ml、36/10(6)脾细胞,P<0.05)、DC组(71.3 pg/ml、10.5 ng/ml、21/10(6)脾细胞,P<0.05)、PBS组(65.8 pg/ml、7.4 ng/ml、18/10(6)脾细胞,P<0.05)强得多且高得多。在预防和治疗实验中,Ad-mTERT/DCs免疫的小鼠存活时间明显长于其他组,表明原代DCs经基因改造表达mTERT抗原并可抑制肿瘤生长。
腺病毒载体介导mTERT感染的DCs能有效诱导mTERT抗原特异性抗肿瘤活性,并能诱导保护性和治疗性抗肿瘤免疫。