P1-01-07: ErbB-2 Peptide Vaccination Suppresses Spontaneous Tumorigenesis and Tumor Stem Cell Expansion in MMTV-PyVT Transgenic Mouse.

Abstract

Abstract Immunization targeting ErbB-2 could have considerable therapeutic potential by controlling growth and metastasis of highly aggressive tumor cells in the earlier preclinical and clinical studies. Just a few studies have examined preventive potential of ErbB-2 vaccines in preclinical studies. However, animal model systems used in the previous studies were tumor transplantation or neu-transgenic mouse, which were not relevant to human HER-2 positive breast tumorigenesis. In this study, active immunotherapy against tumor antigen ErbB-2/neu for primary prevention of breast cancer was tested using FVB/N-Tg (MMTV-PyVT) transgenic mice model. Mice were grouped to receive either ErbB-2 peptide vaccine, immune adjuvant only, tetanus toxoid, or PBS every 2 weeks for 3 times and monthly thereafter. The MMTV-PyVT transgenic mice in control groups (PBS, immune adjuvant only, or tetanus toxoid peptide) developed spontaneous mammary adenocarcinomas in 12 to 15 weeks, but vaccination against ErbB-2 strongly suppressed tumor formation by 30 weeks of observation. Further pathologic examination showed complete prevention of tumorigenesis was observed in ErbB-2 vaccinated mice, whereas the mice in control groups developed highly aggressive ErbB-2 overexpressing tumors similar to human breast cancer. The tumor protective effect of peptide vaccination was associated with induction of ErbB-2-specific humoral immune responses as well as T cell responses. Additionally, role of signal through ErbB-2 pathway and the relationship with stemness of cancer cells were determined by Aldefluor assay, mammosphere formation assay using Mouse mammary carcinoma (MMC) cells in vitro, and level of nestin expression determined by Western blot analysis. Further analysis of mammosphere formation capacity of MMC cells using immune sera showed that sera from ErbB2 vaccinated mice had a significant inhibitory effect on mammosphere formation in ErbB-2 overexpressing MMC cells. These results suggest that ErbB-2 targeting by cancer vaccination might be useful adjuvant to standard therapy, helping to prevent relapse in patients with ErbB-2-overexpressing tumors by suppressing stem/progenitor cell population. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-07.