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01-08-2006

Investigating the Combination of Trastuzumab and HER2/neu Peptide Vaccines for the Treatment of Breast Cancer

Authors: Elizabeth A. Mittendorf, MD, Catherine E. Storrer, BS, Craig D. Shriver, MD, Sathibalan Ponniah, PhD, George E. Peoples, MD

Published in: Annals of Surgical Oncology | Issue 8/2006

Abstract

Background

Trastuzumab, an anti-HER2/neu monoclonal antibody, is thought to promote HER2/neu receptor internalization and/or turnover. This study was designed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte–mediated lysis.

Methods

Three cell lines with varying levels of HER2/neu expression were incubated with varying doses of trastuzumab at multiple time points. Trastuzumab binding and HER2/neu expression were determined. Peripheral blood mononuclear cells from three HLA-A2⁺ healthy donors and four E75 peptide–vaccinated patients were stimulated with HER2/neu-derived peptides and tested in standard chromium release cytotoxicity assays with HER2/neu⁺ tumor cells pretreated with trastuzumab.

Results

Treatment of tumor cells with 10 μg/mL of trastuzumab in an overnight incubation resulted in saturation of cell-surface HER2/neu receptors. At higher doses, trastuzumab staining and HER2/neu expression decreased in a time-dependent manner. Pretreatment of tumor cells with trastuzumab resulted in increases in specific cytotoxicity by peptide-stimulated cytotoxic T lymphocytes from HLA-A2⁺ donors over untreated cells by an average of 5.6% and 15.3% (P = .0002) for doses of 10 and 50 μg/mL, respectively. In similar experiments involving peripheral blood mononuclear cells obtained from immunized patients, the average specific cytotoxicity for untreated cells was 34.2% ± 1.3% vs. 40.6% ± 2.5% (P = .035) and 40.7% ± 1.6% (P = .0005) for those treated with 10 and 50 μg/mL, respectively.

Conclusions

Our data suggest that pretreatment of breast cancer cells with trastuzumab induces turnover of the HER2/neu protein and enhanced killing by HER2/neu peptide–stimulated CTLs. This increased lysis occurs regardless of the degree of HER2/neu expression and seems more pronounced in vaccinated patients. These findings support further investigation into the use of combination immunotherapy with trastuzumab and HER2/neu peptide–based vaccines.

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Title: Investigating the Combination of Trastuzumab and HER2/neu Peptide Vaccines for the Treatment of Breast Cancer
Authors: Elizabeth A. Mittendorf, MD
Catherine E. Storrer, BS
Craig D. Shriver, MD
Sathibalan Ponniah, PhD
George E. Peoples, MD
Publication date: 01-08-2006
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 8/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/ASO.2006.03.069

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Investigating the Combination of Trastuzumab and HER2/neu Peptide Vaccines for the Treatment of Breast Cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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