Induction of antigen-specific CTL and antibody responses in mice by a novel recombinant tandem repeat DNA vaccine targeting at mucin 1 of pancreatic cancer

Induction of antigen-specific CTL and antibody responses in mice by a novel recombinant tandem repeat DNA vaccine targeting at mucin 1 of pancreatic cancer
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通过针对胰腺癌粘蛋白 1 的新型重组串联重复 DNA 疫苗诱导小鼠抗原特异性 CTL 和抗体反应

DOI:
10.1007/s00432-010-0845-4
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发表时间:
2010-03
影响因子:
3.6
通讯作者:
Wang, Dan-Song
Wang, Dan-Song
中科院分区:
医学3区
文献类型:
--
作者:
Wu, Wen-Chuan;Lou, Wen-Hui;Jin, Da-Yong;Qin, Xin-Yu;Wang, Dan-Song

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目的串联重复序列(TR)是粘蛋白1(MUC 1)诱导细胞毒性T淋巴细胞(CTL)特异性杀伤肿瘤细胞的关键表位。材料与方法合成重组人TR(rhTR),构建重组质粒pcDNA3.1-TR/Myc-his(+)A(pTR质粒),免疫C57 BL/6(H-2b)小鼠(TR组,n= 15)。以空载体组(EV组,n= 15)和生理盐水组(NS组,n= 15)分别作为载体和空白对照。细胞毒实验检测CTL活性。结果TR组对TR多肽的CTL特异性杀伤作用明显强于EV组和NS组(P均< 0.01);疫苗免疫的小鼠具有更高的抗TR特异性抗体当量浓度(2,324 ± 238)μg/ml(1,896 ± 533 μg/ml,P< 0.01);(1,736 ± 142 μg/ml,P< 0.01)。结论成功构建了以胰腺癌MUC 1为靶点的重组TR DNA疫苗。在转染的哺乳动物细胞中有效表达TR多肽并诱导TR特异性CTL和抗体应答。
PurposeTandem repeat (TR) is the key epitope of mucin 1 (MUC1) for inducing cytotoxic T lymphocytes (CTL) to kill the tumor cells specifically. This study aimed to construct a new recombinant DNA vaccine based on single TR and to investigate the induced immune responses in mice.Materials and methodsAfter the synthesis of a recombinant human TR(rhTR)and the construction of the recombinant plasmid pcDNA3.1-TR/Myc-his (+) A (pTR plasmid), C57BL/6 (H-2b) mice were immunized with it (TR group,n= 15). Mice inoculated with the empty vector (EV group,n= 15) and normal saline (NS group,n= 15) were used as vector and blank control, respectively. Cytotoxic assay was carried out to measure the CTL activity. And indirect enzyme-linked immunosorbent assay (ELISA) was used to detect anti-TR-specific antibodies.ResultsTR group resulted in more efficient induction of CTL-specific cytolysis against TR polypeptide than both EV and NS groups (bothP< 0.01). Vaccine-immunized mice had a higher equivalent concentration of anti-TR-specific antibodies (2,324 ± 238 μg/ml) than either of EV group (1,896 ± 533 μg/ml,P< 0.01) or NS group (1,736 ± 142 μg/ml,P< 0.01).ConclusionThe novel recombinant TR DNA vaccine targeting at MUC1 of pancreatic cancer was constructed successfully, effectively expressing TR polypeptide in the transfected mammalian cells and inducing TR-specific CTL and antibody response.
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发表时间: 2003
影响因子: 4.4
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