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Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice.

机译:携带人端粒酶肿瘤抗原的重组慢病毒载体在HLA-B * 0702转基因小鼠中的免疫原性。

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Over expression of telomerase represents a hallmark of cancer cells and the induction of T cell immunity against this universal tumor antigen have gained promising interest for anticancer immunotherapy. In this study we evaluated a recombinant lentiviral vector expressing the human telomerase reverse transcriptase (lv-hTERT) vaccination in the humanized HLA-B*0702 transgenic (HLA-B7 Tg) mice. A single lv-hTERT vector immunization induces potent and broad HLA-B7-restricted CTL responses against hTERT. Unlike conventional hTERT peptide or DNA immunization, the lv-hTERT vector triggers high and sustained IFN- gamma producing CD8+ T cell responses in HLA-B7 Tg mice. The avidity and in vivo cytotoxicity of CD8+ T cells were stronger in lv-hTERT vector-immunized mice than in hTERT peptide or DNA vaccinated groups. The study also showed that the use of prime-boost vaccination drastically improved the magnitude and strength of lentivector-primed CD8+ T cells. Our data indicated that lentiviral delivery of hTERT is suitable for enhancing cellular immunity against hTERT and offers a promising alternative for telomerase-based cancer vaccine.
机译:端粒酶的过度表达代表癌细胞的特征,针对这种通用肿瘤抗原的T细胞免疫诱导已引起抗癌免疫治疗的广泛兴趣。在这项研究中,我们评估了在人源化HLA-B * 0702转基因(HLA-B7 Tg)小鼠中表达人端粒酶逆转录酶(lv-hTERT)疫苗接种的重组慢病毒载体。单个lv-hTERT载体免疫可诱导针对hTERT的有效且广泛的HLA-B7限制性CTL反应。与常规的hTERT肽或DNA免疫不同,lv-hTERT载体在HLA-B7 Tg小鼠中触发高而持续的IFN-γ产生CD8 + T细胞反应。在lv-hTERT载体免疫的小鼠中,CD8 + T细胞的亲和力和体内细胞毒性要强于hTERT肽或DNA疫苗接种组。研究还表明,使用初免-加强接种可以大大提高慢病毒载体启动的CD8 + T细胞的大小和强度。我们的数据表明,hTERT的慢病毒递送适合增强针对hTERT的细胞免疫力,并为基于端粒酶的癌症疫苗提供了有希望的替代方法。

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