Prophylactic vaccination targeting ERBB3 decreases polyp burden in a mouse model of human colorectal cancer
Prophylactic vaccination targeting ERBB3 decreases polyp burden in a mouse model of human colorectal cancer
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DOI：
10.1080/2162402x.2016.1255395
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Threadgill, David W.
中科院分区：
文献类型：
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作者：
Bautz, David J.;Sherpa, Ang T.;Threadgill, David W.
预防性疫苗接种通常用于预防麻疹和流感等传染病，但除了预防宫颈癌的疫苗外，并未广泛用作预防或减少癌症发病率的手段。在这里，我们利用一种针对ERBB3的基于多肽的免疫治疗方法，作为预防结肠息肉发生的一种手段。ERBB3是EGFR/ERBB受体酪氨酸激酶家族中的一个假性激酶成员。在家族性腺瘤性息肉病(FAP)模型C57BL/6J-APC(Min)小鼠肠息肉的发生过程中，给予该多肽可显著降低小鼠的肠息肉发生率。此外，即使没有接种疫苗，接种疫苗女性所生的APC(Min)后代患息肉的比例明显低于对照女性所生的后代。最后，为了验证ERBB作为疫苗接种的有效靶点，我们在成年小鼠中没有发现ErB3被消融的组织中明显的毒性、细胞凋亡的增加或形态变化。这些结果表明，针对ERBB3的预防性疫苗接种可以防止高危患者人群中结肠息肉的发展。
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-Apc(Min) mice, a model of familial adenomatous polyposis (FAP). In addition, even though they were not vaccinated, Apc(Min) offspring born to vaccinated females developed significantly fewer polyps than offspring born to control females. Lastly, to validate ERBB as a valid target for vaccination, we found no overt toxicity, increases in apoptosis, or morphological changes in tissues where Erbb3 was ablated in adult mice. These results indicate that prophylactic vaccination targeting ERBB3 could prevent the development of colon polyps in an at-risk patient population.