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首页> 外文期刊>Vaccine >Co-expression of Flt-3 ligand gene ablates tumor immunity elicited by HER-2eu DNA vaccine in transgenic mice
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Co-expression of Flt-3 ligand gene ablates tumor immunity elicited by HER-2eu DNA vaccine in transgenic mice

机译：Flt-3配体基因的共表达可消除HER-2 / neu DNA疫苗在转基因小鼠中引起的肿瘤免疫力

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摘要

Fms-like tyrosine-kinase 3 ligand (Flt-3L), is a powerful hematopoyetic growth factor, known to modulate the immune response against delivered antigens by acting either as an adjuvant or tolerogenic stimulus. In this study we evaluated the use of murine Flt-3 ligand plasmid (pFI) in combination with a DNA vaccine encoding rat-p185 oncoprotein extra cellular domain (pECD) in the prevention of mammary carcinogenesis in rat-neu HER-2 mutated (neuT) transgenic mice. We demonstrate that intramuscular (i.m.) co-immunization of pFI inhibits the production of anti-HER-2 antibody elicited by pECD vaccine, resulting in the development of spontaneous carcinomas in all co-immunized mice. The inhibitory effect on antibody production by mFlt3 gene appeared to be: dose-dependent, linked to the injection site and timing, and transient in nature. Additionally, we show that co-administration of pFI and pECD plasmids was unable to trigger cytotoxic T-cell immune response in neuT mice. On the other hand, we found that the combination of pFI with pECD had no impact on the ability of pECD to reject HER-2+ transplantable tumors in parental mice. In summary our results demonstrate that, depending on tumor model, co-administration of pFI gene can produce untoward effects to immune response, and thus its application as a vaccine adjuvant should be carefully evaluated.
机译：Fms样酪氨酸激酶3配体（Flt-3L）是一种强大的造血生长因子，已知其通过充当佐剂或致耐受性刺激物来调节针对递送抗原的免疫反应。在这项研究中，我们评估了将鼠Flt-3配体质粒（pFI）与编码大鼠p185癌蛋白胞外域（pECD）的DNA疫苗联合用于预防大鼠中性HER-2突变（neuT）的乳腺癌致癌作用。 ）转基因小鼠。我们证明pFI的肌内（i.m.）联合免疫抑制了pECD疫苗引起的抗HER-2抗体的产生，导致所有联合免疫小鼠中自发性癌的发展。 mFlt3基因对抗体产生的抑制作用似乎是：剂量依赖性的，与注射部位和时机有关，并且本质上是瞬时的。此外，我们显示pFI和pECD质粒的共同给药无法在neuT小鼠中触发细胞毒性T细胞免疫应答。另一方面，我们发现pFI和pECD的组合对亲本小鼠中pECD拒绝HER-2 +可移植肿瘤的能力没有影响。总之，我们的结果表明，根据肿瘤模型的不同，共同施用pFI基因可能会对免疫反应产生不良影响，因此应仔细评估其作为疫苗佐剂的应用。

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