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Experimental Therapeutics, Molecular Targets, and Chemical Biology |
1 Vaccine Branch and 2 Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and 3 Molecular Biotechnology Center, Clinical and Biological Sciences, University of Turin, Turin, Italy
Requests for reprints: Masaki Terabe, National Cancer Institute, NIH, Building 10, Room 6B-12, 9000 Rockville Pike, Bethesda, MD 20892-1578. Phone: 301-435-8349; Fax: 301-402-0549; E-mail: terabe{at}mail.nih.gov.
Key Words: Advanced cancer Breast cancer Vaccine therapy
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. [Cancer Res 2008;68(6):1979–87]
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