Treating cancer as an infectious disease--viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology.
Treating cancer as an infectious disease--viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology.
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DOI：
10.1371/journal.pone.0001114
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发表时间：
2007-10-31
期刊：
影响因子：
3.7
通讯作者：
Dadachova E
中科院分区：
文献类型：
--
作者：
Wang XG;Revskaya E;Bryan RA;Strickler HD;Burk RD;Casadevall A;Dadachova E
全世界近20%的人类癌症具有感染性病因，最突出的例子是乙型和丙型肝炎病毒相关的肝细胞癌和人类乳头瘤病毒相关的宫颈癌。迫切需要找到治疗和预防病毒相关癌症的新方法。病毒抗原以前没有被认为是治疗或预防病毒相关癌症的靶点。我们假设有可能通过用放射性标记的病毒抗原抗体靶向癌细胞上表达的病毒抗原来治疗实验性hpv16相关宫颈癌（CC）和乙型肝炎相关肝细胞癌（HCC）。用188re标记的针对E6和HBx病毒蛋白的单克隆抗体分别治疗实验性CC和HCC肿瘤，与未治疗的小鼠或未标记抗体治疗的小鼠相比，肿瘤生长阻滞显著且呈剂量依赖性。这一策略与肿瘤放射免疫治疗的先前使用有着根本的不同，放射免疫治疗针对肿瘤相关的人类抗原，并承诺提高特异性和最小的毒性治疗。它还提出了一种令人兴奋的可能性，即通过在感染致癌病毒的细胞转化为癌症之前消除它们，来预防慢性感染患者的病毒相关癌症。
Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers. Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC) and Hepatitis B-associated hepatocellular carcinoma (HCC) by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with 188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies. This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.
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影响因子：
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