HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH Cancer Research Clinical Cancer Research Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics Molecular Cancer Research Cancer Prevention Research Cancer Prevention Journals Portal Cancer Reviews Online Annual Meeting Education Book Meeting Abstracts Online		QUICK SEARCH:   [advanced] Author: Keyword(s):

This Article Services Similar articles in this journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Czerniecki, B. J. Articles by Koski, G. Search for Related Content PubMed Articles by Czerniecki, B. J. Articles by Koski, G.

Proffered Abstract (Oral Presentation): Immunoprevention of Cancer: Future, Not Fantasy

Targeted immunoediting of critical pathways responsible for breast cancer development: Treatment of early breast cancer using HER-2/neu pulsed dendritic cells.

University of Pennsylvania, Philadelphia, PA; Cleveland Clinic, Cleveland, OH

Abstract

PR-03

HER-2/neu over-expression plays a critical role in breast cancer development occurring in about 50-60% of high grade ductal carcinomas in situ (DCIS) lesions in the breast. HER-2/neu expression in DCIS predicts increased risk of recurrence and can often provide an escape pathway in patients treated with anti-estrogen therapy. Developing cancer vaccines targeting HER-2/neu may therefore potentially prevent a significant number of breast cancers. Patients with HER-2/neu over-expressing DCIS were invited to participate in a neoadjuvant vaccine study using HER-2/neu pulsed dendritic cells (DC). Type I polarized DC secreting high levels of IL-12 were prepared under IND BB-11043 using interferon gamma and the toll receptor 4 agonist lipopolysacharide (LPS). The DC were pulsed with 6 MHC class II binding peptides and for HLA A2+ patients the DC were also pulsed with MHC class I binding peptides. The patients received 4 weekly intranodal vaccinations consisting of 10-20 million DC. Immune assessment, HER-2/neu expression and cellular infiltrates were conducted pre and post-vaccination. Despite the presence of tolerant T cells pre-vaccine, anti-HER-2/neu specific Th1 CD4+ T cells were detected in 11 of 12 patients' peripheral blood and in sentinel nodes of 10 patients. HER-2/neu specific CD8+ T cells developed in six of eight HLA A2+ patients. These CD8+ T cells were able to recognize HER-2/neu expressing breast cancer cells. Anti-HER-2/neu complement fixing antibodies were frequently detected post-vaccination and anti-human antibodies could be detected bound to DCIS post-vaccination as well. Lymphocytic infiltrates consisting predominately of CD4 and B cells accumulated in the breast following vaccination. Both humoral and cellular anti-HER-2/neu responses could be detected for prolonged periods following vaccinations. Six of twelve patients (50%) demonstrated dramatic reductions in HER-2/neu expression post-vaccination in residual DCIS and there were associated apparent reductions in the extent of DCIS in half of the patients as well. These results demonstrate HER-2/neu pulsed type I polarized DC lead to both cellular and humoral immune activation and demonstrating for the first time a DC vaccine with significant clinical activity. Targeted immunoediting HER-2/neu using cancer vaccines may therefore be useful not only for treatment of DCIS but may also play a role in the prevention of breast cancer development.