Strengthened tumor antigen immune recognition by inclusion of a recombinant Eimeria antigen in therapeutic cancer vaccination.
Strengthened tumor antigen immune recognition by inclusion of a recombinant Eimeria antigen in therapeutic cancer vaccination.
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通过在治疗性癌症疫苗接种中加入重组艾美耳球虫抗原，增强了肿瘤抗原的免疫识别。
DOI：
10.1007/s00262-015-1659-7
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Amalfitano,Andrea
中科院分区：
文献类型：
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作者：
Quiroga,Dionisia;Aldhamen,YasserA;Appledorn,DanielM;Godbehere,Sarah;Amalfitano,Andrea
在疫苗开发领域中，对能够引发对抗原靶标的更强的细胞和体液适应性免疫应答的新型有效佐剂的需求是众所周知的。不幸的是，迄今为止研究的许多佐剂对于人类应用来说毒性太大，或者太弱而不能诱导针对困难抗原（如肿瘤相关抗原（TAA））的实质性应答。尽管存在这种趋势，但对重组艾美耳球虫抗原（rEA）的临床研究已经揭示了这种蛋白质是一种无毒的免疫原性试剂，具有在鼠和人受试者中触发Th 1-优势应答的能力。我们过去的研究表明，注射rEA编码腺病毒（rAd 5-rEA）与HIV抗原编码腺病毒一起大大提高了针对这种病原体衍生转基因的适应性免疫应答。在这份报告中，我们调查是否rAd 5-rEA可以促进和/或改变细胞毒性记忆反应对癌胚抗原（CEA），结直肠癌相关的TAA。我们发现，向基于Ad的CEA疫苗中添加rAd 5-rEA可诱导几种抗CEA T和B细胞反应呈剂量依赖性增加。此外，包含rAd 5-rEA增加了CEA衍生的抗原表位的数量，引起显着的细胞介导的和IgG介导的识别。这些增强的抗CEA免疫应答也转化为上级CEA靶向细胞杀伤，如通过体内细胞毒性T淋巴细胞测定所评估的。总体而言，这些结果表明，rAd 5-rEA与肿瘤抗原疫苗的共施用可以显著增强和扩大TAA特异性适应性记忆应答，从而验证rAd 5-rEA在治疗性癌症疫苗接种期间作为有益佐剂的潜力。
The need for novel, effective adjuvants that are capable of eliciting stronger cellular and humoral adaptive immune responses to antigenic targets is well understood in the vaccine development field. Unfortunately, many adjuvants investigated thus far are either too toxic for human application or too weak to induce a substantial response against difficult antigens, such as tumor-associated antigens (TAAs). In spite of this trend, clinical investigations of recombinantEimeriaantigen (rEA) have revealed this protein to be a non-toxic immunogenic agent with the ability to trigger a Th1-predominant response in both murine and human subjects. Our past studies have shown that the injection of a rEA-encoding adenovirus (rAd5-rEA) alongside an HIV antigen-encoding adenovirus greatly improves the adaptive immune response against this pathogen-derived transgene. In this report, we investigated whether rAd5-rEA could promote and/or alter cytotoxic memory responses toward carcinoembryonic antigen (CEA), a colorectal cancer-related TAA. We found that the addition of rAd5-rEA to an Ad-based CEA vaccine induced a dose-dependent increase in several anti-CEA T and B cell responses. Moreover, inclusion of rAd5-rEA increased the number of CEA-derived antigenic epitopes that elicited significant cell-mediated and IgG-mediated recognition. These enhanced anti-CEA immune responses also translated into superior CEA-targeted cell killing, as evaluated by an in vivo cytotoxic T lymphocyte assay. Overall, these results suggest that co-administration of rAd5-rEA with a tumor antigen vaccine can substantially boost and broaden the TAA-specific adaptive memory response, thereby validating the potential of rAd5-rEA to be a beneficial adjuvant during therapeutic cancer vaccination.