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首页> 外文期刊>The Journal of Immunology: Official Journal of the American Association of Immunologists >An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2eu+ breast tumors in a mouse model.
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An anti-vascular endothelial growth factor receptor 2/fetal liver kinase-1 Listeria monocytogenes anti-angiogenesis cancer vaccine for the treatment of primary and metastatic Her-2eu+ breast tumors in a mouse model.

机译：一种抗血管内皮生长因子受体2 /胎儿肝激酶-1单核细胞增生李斯特菌抗血管生成癌症疫苗，用于治疗小鼠模型中的原发性和转移性Her-2 / neu +乳腺肿瘤。

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Thirty years after angiogenesis was shown to play an enabling role in cancer, modern medicine is still trying to develop novel compounds and therapeutics to target the tumor vasculature. However, most therapeutics require multiple rounds of administration and can have toxic side effects. In this study, we use anti-angiogenesis immunotherapy to target cells actively involved in forming new blood vessels that support the growth and spread of breast cancer. Targeting a central cell type involved in angiogenesis, endothelial cells, we immunized against host vascular endothelial growth factor receptor 2 to fight the growth of Her-2eu(+) breast tumors. Using the bacterial vector, Listeria monocytogenes (Lm), we fused polypeptides from the mouse vascular endothelial growth factor receptor 2 molecule (fetal liver kinase-1) to the microbial adjuvant, listeriolysin-O, and used Lm to deliver the Ags and elicit potent antitumor CTL responses. Lm-listeriolysin-O-fetal liver kinase-1 was able to eradicate some established breast tumors, reduce microvascular density in the remaining tumors, protect against tumor rechallenge and experimental metastases, and induce epitope spreading to various regions of the tumor-associated Ag Her-2eu. Tumor eradication was found to be dependent on epitope spreading to HER-2eu and was not solely due to the reduction of tumor vasculature. However, vaccine efficacy did not affect normal wound healing nor have toxic side effects on pregnancy. We show that an anti-angiogenesis vaccine can overcome tolerance to the host vasculature driving epitope spreading to an endogenous tumor protein and drive active tumor regression.
机译：血管生成已被证明在癌症中起着重要作用三十年，现代医学仍在尝试开发针对肿瘤脉管系统的新型化合物和疗法。但是，大多数治疗方法需要多轮给药，并且可能有毒副作用。在这项研究中，我们使用抗血管生成免疫疗法靶向积极参与形成新血管的细胞，这些新血管支持乳腺癌的生长和扩散。针对涉及血管生成的中心细胞类型，内皮细胞，我们针对宿主血管内皮生长因子受体2进行了免疫，以对抗Her-2 / neu（+）乳腺肿瘤的生长。使用细菌载体单核细胞增生性李斯特菌（Lm），我们将小鼠血管内皮生长因子受体2分子（胎儿肝激酶1）的多肽融合到微生物佐剂李斯特菌溶血素O中，并使用Lm递送Ags并诱导有效抗肿瘤CTL反应。 Lm-李斯特菌溶血素-O-胎肝激酶1能够根除一些已确定的乳腺肿瘤，降低其余肿瘤中的微血管密度，防止肿瘤再发和实验性转移，并诱导抗原决定簇扩散到与肿瘤相关的Ag Her的各个区域-2 / neu。发现根除肿瘤取决于表位扩散到HER-2 / neu，而不仅仅是由于肿瘤脉管系统的减少。但是，疫苗的功效不会影响正常的伤口愈合，也不会对怀孕产生毒性副作用。我们表明，抗血管生成疫苗可以克服对宿主脉管系统的驱动力，将表位扩展至内源性肿瘤蛋白，并促进肿瘤的消退。

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