Induction of effective therapeutic antitumor immunity by direct in vivo administration of lentiviral vectors
Induction of effective therapeutic antitumor immunity by direct in vivo administration of lentiviral vectors
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DOI：
10.1038/sj.gt.3302697
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发表时间：
2006-04-01
期刊：
影响因子：
5.1
通讯作者：
Breckpot, K
中科院分区：
文献类型：
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作者：
Dullaers, M;Van Meirvenne, S;Breckpot, K
体外慢病毒转导的树突状细胞（DC）已经被描述为在体外和体内诱导CD8（+）和CD4(+) t细胞对各种肿瘤相关抗原（TAAs）的反应。我们在此报道，直接给药编码慢病毒载体的卵清蛋白（OVA）导致引流淋巴结（LNs）中发现的细胞在体内转导，并诱导类似于体外转导DC诱导的有效抗卵清蛋白细胞毒性T细胞。直接注射慢病毒载体后的细胞毒性t淋巴细胞（CTL）反应在免疫后30天内非常有效地消除体内靶细胞，并在增强免疫后有效地召回。注射慢病毒载体进一步激活ova特异性CD4(+) T细胞，这种CD4帮助被证明是充分的初级和记忆CTL反应所必需的。在OVA（+）黑色素瘤细胞的治疗性肿瘤实验中，直接使用慢病毒载体减缓肿瘤生长的程度与最高剂量的体外转导DC相当。综上所述，这些数据表明直接在体内给药编码TAAs的慢病毒载体具有很强的抗癌疫苗接种潜力。
Ex vivo lentivirally transduced dendritic cells ( DC) have been described to induce CD8(+) and CD4(+) T-cell responses against various tumor-associated antigens (TAAs) in vitro and in vivo. We report here that direct administration of ovalbumin ( OVA) encoding lentiviral vectors caused in vivo transduction of cells that were found in draining lymph nodes (LNs) and induced potent anti-OVA cytotoxic T cells similar to those elicited by ex vivo transduced DC. The cytotoxic T-lymphocyte (CTL) response following direct injection of lentiviral vectors was highly effective in eliminating target cells in vivo up to 30 days after immunization and was efficiently recalled after a boost immunization. Injection of lentiviral vectors furthermore activated OVA-specific CD4(+) T cells and this CD4 help was shown to be necessary for an adequate primary and memory CTL response. When tested in therapeutic tumor experiments with OVA(+) melanoma cells, direct administration of lentiviral vectors slowed down tumor growth to a comparable extent with the highest dose of ex vivo transduced DC. Taken together, these data indicate that direct in vivo administration of lentiviral vectors encoding TAAs has strong potential for anticancer vaccination.