A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors.
A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors.
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DOI：
10.1007/s10456-012-9263-3
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发表时间：
2012-06
期刊：
影响因子：
9.8
通讯作者：
Cavallo, Federica
中科院分区：
文献类型：
--
作者：
Arigoni, Maddalena;Barutello, Giuseppina;Lanzardo, Stefania;Longo, Dario;Aime, Silvio;Curcio, Claudia;Iezzi, Manuela;Zheng, Yujuan;Barkefors, Irmeli;Holmgren, Lars;Cavallo, Federica
血管动素（Amot）是由血管生成组织的内皮细胞表达的几种经鉴定的血管抑素受体之一。我们已经证明，靶向Amot的DNA疫苗克服了免疫耐受，并诱导了阻碍早期肿瘤进展的抗体应答。在我们观察到肿瘤内皮细胞上Amot表达增加伴随着从肿瘤前病变到完全成熟的癌的进展之后，我们评估了抗Amot疫苗接种对临床上明显的肿瘤的影响。电穿孔编码人Amot（pAmot）的质粒显著延迟了易患癌症的BALB-neuT和PyMT基因工程小鼠中的自体肿瘤和野生型BALB/c小鼠中的可移植TUBO肿瘤的进展。抑制的强度与疫苗诱导的抗Amot抗体的滴度直接相关。肿瘤抑制与血管直径增加、腔隙形成、血管通透性增加、大量肿瘤血管周围坏死和有效表位扩散相关，该表位扩散诱导针对其他肿瘤相关抗原的免疫应答。更大的肿瘤血管渗透性也显著增强阿霉素的抗肿瘤作用。这些数据为基于抗Amot疫苗接种联合化疗方案开发新型抗癌治疗提供了依据。本文的在线版本（doi：10.1007/s10456-012-9263-3）包含补充材料，可供授权用户使用。
Angiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. We have shown that a DNA vaccine targeting Amot overcome immune tolerance and induce an antibody response that hampers the progression of incipient tumors. Following our observation of increased Amot expression on tumor endothelia concomitant with the progression from pre-neoplastic lesions to full-fledged carcinoma, we evaluated the effect of anti-Amot vaccination on clinically evident tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. Greater tumor vessel permeability also markedly enhances the antitumor effect of doxorubicin. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens. The online version of this article (doi:10.1007/s10456-012-9263-3) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.bbamcr.2007.11.018
发表时间：
2008-03-01
影响因子：
5.1
作者：
Ernkvist, Mira;Birot, Olivier;Holmgren, Lars
通讯作者：
Holmgren, Lars
影响因子：
33.6
作者：
Goel S;Duda DG;Xu L;Munn LL;Boucher Y;Fukumura D;Jain RK
通讯作者：
Jain RK
影响因子：
6
作者：
Lin, EY;Jones, JG;Pollard, JW
通讯作者：
Pollard, JW
影响因子：
82.9
作者：
HOLMGREN, L;OREILLY, MS;FOLKMAN, J
通讯作者：
FOLKMAN, J
影响因子：
45.3
作者：
Hahn, Olwen M.;Yang, Cheng;Stadler, Walter M.
通讯作者：
Stadler, Walter M.