Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases.
Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases.
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重组单核细胞增生李斯特菌提供的MAGE-B疫苗对乳腺癌转移非常有效。
DOI：
10.1038/sj.bjc.6604526
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发表时间：
2008-09-02
影响因子：
8.8
通讯作者：
Gravekamp, C.
中科院分区：
文献类型：
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作者：
Kim, S. H.;Castro, F.;Gonzalez, D.;Maciag, P. C.;Paterson, Y.;Gravekamp, C.
需要针对乳腺癌转移的新疗法。在以前的研究中，我们已经表明，pcDNA3.1-Mage-b DNA疫苗接种对乳腺癌转移是有效的。在这里介绍的研究中，我们通过使用重组单核细胞增生李斯特菌（LM）改进疫苗的递送，进一步增强了Mage-b疫苗接种的功效。Mage-b的三个重叠片段以及Mage-b的完整蛋白编码区已在重组LM中表达为具有截短的非细胞溶解形式的鲎溶血素O（LLO）的融合蛋白。在同基因小鼠肿瘤模型4 T1中，对这些不同的Mage-b疫苗株进行了预防性测试，以确定其对乳腺癌转移的有效性。LM-LLO-Mage-b/2nd表达Mage-b cDNA的311-660位，是4 T1小鼠乳腺肿瘤模型中针对转移的最有效疫苗株。与生理盐水组相比，用LM-LLO-Mage-b/2nd疫苗接种显著减少了96%的转移瘤数量，与载体对照组（LM-LLO）相比，显著减少了88%的转移瘤数量，这与用Mage-b再刺激后脾脏中的强Mage-b特异性CD 8 T细胞应答相关。然而，在4 T1原发性肿瘤上没有观察到LM-LLO-Mage-b/2nd的作用，这可能是引流淋巴结中完全不存在Mage-b特异性免疫应答的结果。LM-LLO-Mage-b/2nd疫苗接种可能是原发性肿瘤切除后的一种极好的随访，以消除转移和残留的肿瘤细胞。
New therapies are needed that target breast cancer metastases. In previous studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is effective against breast cancer metastases. In the study presented here, we have further enhanced the efficacy of Mage-b vaccination through the improved delivery of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping fragments of Mage-b as well as the complete protein-encoding region of Mage-b have been expressed as a fusion protein with a truncated non-cytolytic form of listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains were preventively tested for their efficacy against breast cancer metastases in a syngeneic mouse tumour model 4T1. The LM-LLO-Mage-b/2nd, expressing position 311–660 of the cDNA of Mage-b, was the most effective vaccine strain against metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage-b/2nd dramatically reduced the number of metastases by 96% compared with the saline group and by 88% compared with the vector control group (LM-LLO), and this correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed on 4T1 primary tumours, which may be the result of a complete absence of Mage-b-specific immune responses in the draining lymph nodes. Vaccination with LM-LLO-Mage-b/2nd could be an excellent follow-up after removal of the primary tumour, to eliminate metastases and residual tumour cells.
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影响因子：
3.2
作者：
Gravekamp, C;Sypniewska, R;Reddick, R
通讯作者：
Reddick, R
影响因子：
4.4
作者：
DEBACKER, O;VERHEYDEN, AM;BOON, T
通讯作者：
BOON, T
影响因子：
4.4
作者：
DiPaolo, Richard J.;Brinster, Carine;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
8.4
作者：
Marchand, M;Punt, CJA;Stoter, G
通讯作者：
Stoter, G
DOI：
10.1046/j.1524-4733.2000.31003.x
发表时间：
2000-01-01
期刊：
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research
影响因子：
--
作者：
Berkowitz, N;Gupta, S;Silberman, G
通讯作者：
Silberman, G