Park Jong Myun, Terabe Masaki, Steel Jason C, Forni Guido, Sakai Yoshio, Morris John C, Berzofsky Jay A
Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1578, USA.
Cancer Res. 2008 Mar 15;68(6):1979-87. doi: 10.1158/0008-5472.CAN-07-5688.
ErbB-2 (HER-2/neu) is a transforming oncogene expressed by a substantial fraction of breast cancers, and monoclonal antibody therapy directed toward this antigen is an established treatment modality. However, not all tumors respond, and with a monoclonal antibody directed to a single epitope, there is always the risk of tumor escape. Furthermore, passive antibody therapy requires continual treatment. Whereas cancer vaccines have prevented the growth of tumors, it has been far more difficult to treat large established tumors. Here, we show that vaccination with a recombinant adenovirus expressing a truncated ErbB-2 antigen can cure large established subcutaneous ErbB-2-expressing breast cancers in mice, and can also cure extensive established lung metastatic disease. We also show that the mechanism of protection involves antibody-mediated blockade of ErbB-2 function, independent of Fc receptors. We conclude that a vaccine inducing antibodies to a functional oncogenic receptor could have tremendous therapeutic potential against cancers overexpressing such molecules.
ErbB-2（HER-2/neu）是一种在相当一部分乳腺癌中表达的转化癌基因，针对该抗原的单克隆抗体疗法是一种既定的治疗方式。然而，并非所有肿瘤都会产生反应，并且使用针对单一表位的单克隆抗体时，始终存在肿瘤逃逸的风险。此外，被动抗体疗法需要持续治疗。虽然癌症疫苗可以阻止肿瘤生长，但治疗已形成的大型肿瘤要困难得多。在此，我们表明，用表达截短型ErbB-2抗原的重组腺病毒进行疫苗接种可以治愈小鼠体内已形成的大型皮下ErbB-2表达型乳腺癌，还可以治愈广泛的已形成的肺转移疾病。我们还表明，保护机制涉及抗体介导的对ErbB-2功能的阻断，与Fc受体无关。我们得出结论，一种诱导针对功能性致癌受体的抗体的疫苗可能对过表达此类分子的癌症具有巨大的治疗潜力。
