MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model.
MUC1 and survivin combination tumor gene vaccine generates specific immune responses and anti-tumor effects in a murine melanoma model.
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MUC1 和生存素组合肿瘤基因疫苗在小鼠黑色素瘤模型中产生特异性免疫反应和抗肿瘤作用。
DOI：
10.1016/j.vaccine.2016.04.045
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发表时间：
2016
期刊：
影响因子：
5.5
通讯作者：
W. Kong
中科院分区：
文献类型：
--
作者：
Hai;Chenlu Liu;Fangfang Zhang;F. Geng;Q. Xia;Zhenzhen Lu;P. Xu;Yu Xie;H. Wu;Bin Yu;Jiaxin Wu;Xianghui Yu;W. Kong
MUC 1和Survivin是理想的肿瘤抗原。尽管许多靶向生存素或MUC 1的癌症疫苗已进入临床试验，但尚未报道MUC 1和生存素组合的疫苗。由于肿瘤的异质性，含有抗原组合的疫苗可能具有改善的功效和更广泛的癌症靶点的覆盖范围。在此，评价了靶向MUC 1和生存素（MS）的DNA疫苗组合诱导的细胞应答和抗肿瘤活性。结果表明，联合疫苗免疫小鼠后，其CTL活性和抑瘤作用明显增强。然而，为了增强治疗试验中的治疗效果，在DNA疫苗初免后使用表达MUC 1和存活素的重组腺病毒（rAd）疫苗（Ad-MS）作为加强剂。同时，IL-2促进T细胞增殖被用作DNA疫苗的免疫佐剂。结果表明，rAd疫苗可使CTL活性增强近200%，与IL-2佐剂联合使用可使CTL活性进一步增强近60%。因此，DNA初免联合rAd加强和IL-2佐剂（MS/IL 2/Ad-MS）被认为是最佳策略，并进一步评估。MS/IL 2/Ad-MS免疫小鼠后，多种细胞因子促进细胞免疫应答，治疗实验中，MS/IL 2/Ad-MS的抑瘤率高达50.1%，这可能是由于MS/IL 2/Ad-MS增强了荷瘤小鼠的免疫应答，减少了免疫抑制因子。这些结果表明，使用DNA引发-rAd加强策略沿着IL-2佐剂一起用靶向MUC 1和存活素的组合疫苗免疫可能是突破对表达这些抗原的肿瘤的免疫耐受的有效方法，在黑色素瘤癌症中具有潜在的治疗益处。
MUC1 and survivin are ideal tumor antigens. Although many cancer vaccines targeting survivin or MUC1 have entered clinical trials, no vaccine combining MUC1 and survivin have been reported. Due to tumor heterogeneity, vaccines containing a combination of antigens may have improved efficacy and coverage of a broader spectrum of cancer targets. Here, cellular responses and anti-tumor activities induced by a combination of DNA vaccine targeting MUC1 and survivin (MS) were evaluated. Results showed that CTL activity and inhibition of tumor growth were obviously enhanced in mice immunized with the combined vaccine in a protection assay. However, in order to enhance the therapeutic effect in the treatment assay, a recombinant adenovirus (rAd) vaccine expressing MUC1 and survivin (Ad-MS) was used as a booster following the DNA vaccine prime. Meanwhile, IL-2 promoting T cell proliferation was used as an immunoadjuvant for the DNA vaccine. Results showed that the CTL activity response to the DNA vaccine was enhanced nearly 200% when boosted by the rAd vaccine and was further enhanced by nearly 60% when combined with the IL-2 adjuvant. Therefore, DNA prime combined with rAd boost and IL-2 (MS/IL2/Ad-MS) adjuvant was considered as the best strategy and further evaluated. Multiple cytokines promoting cellular immune responses were shown to be greatly enhanced in mice immunized with MS/IL2/Ad-MS. Moreover, in the treatment assay, the tumor inhibition rate of MS/IL2/Ad-MS reached up to 50.1%, which may be attributed to the enhancement of immune responses and reduction of immunosuppressive factors in tumor-bearing mice. These results suggested that immunization with the combination vaccine targeting MUC1 and survivin using a DNA prime–rAd boost strategy along with IL-2 adjuvant may be an effective method for breaking through immune tolerance to tumors expressing these antigens with potential therapeutic benefits in melanoma cancer.
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影响因子：
5.5
作者：
Kamphorst, Alice O.;Araki, Koichi;Ahmed, Rafi
通讯作者：
Ahmed, Rafi
影响因子：
13.6
作者：
Nath S;Mukherjee P
通讯作者：
Mukherjee P
影响因子：
15.9
作者：
Loeffler, Markus;Krueger, Joerg A.;Reisfeld, Ralph A.
通讯作者：
Reisfeld, Ralph A.
从上皮肿瘤抗原粘蛋白的串联重复结构域中鉴定 HLA-A11 限制性表位。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Domenech,N;Henderson,RA;Finn,OJ
通讯作者：
Finn,OJ