Abstract 754: Heat shock protein vaccines for immunotherapy ofHer-2/neu positive breast cancers

Abstract

Abstract Over-expression of Her-2/neu protein, a member of the epidermal growth factor receptor (EGFR) involved in cell growth results in cancer development. 20-30% of breast cancers over-express Her-2/neu protein and this has been correlated with poor prognosis, leading to recurrence after their initial treatment. Thus new strategies are necessary to combat this devastating disease. The selective expression of HER-2/neu in epithelial carcinogenesis makes HER-2/neu antigen an ideal target for immunotherapy. The objective of our research is to explore vaccine strategies that impacts both B and T cell responses in HER-2/neu breast cancer models. We are exploring heat shock proteins (HSP) vaccines that will chaperone tumor-associated antigens including our antigen of interest Her-2/neu protein to elicit innate and adaptive responses. We are utilizing the rat Her-2/neu as our model antigen and are administering these vaccines in transplantable and transgenic her-2/neu murine models after tumor implantation. Our first approach was to generate a Her-2/neu derived HSP gp96 in a secretable form. It has been reported that gp96 can ubiquitously bind to cell associated peptides and cross present these antigens to CD8+ T-cells to generate an effective cytotoxic T cell (CTL) response. Cancer cells expressing rat Her-2/neu were stably transfected with a mouse gp96IgG eukaryotic expression vector, where the endoplasmic retention signal sequence KDEL of gp96 was replaced with the hinge and CH2 and CH3 domains of murine IgG1. 2×104 stably transfected cells secreted within 24h 100- 200ng gp96IgG. Our goal is to generate Her-2/neu specific CD8 T cell responses that would result in vivo tumor delay. Our second approach was to test the adjuvanticity of a mixture of HSPs in combination with irradiated tumor cells. Administration of the vaccine in a therapeutic setting not only delayed tumor growth, but also provided survival benefit. Additionally, vaccinated animals were superior in eliciting Her-2/neu specific antibody response when compared to the HSP vaccine or the irradiated tumor cells alone. Our long-term goal is to combine both approaches to enhance cytotoxic T cell (CTL) and B cell specific response against Her-2/neu specific cancers. Funded by: American Cancer Society MRSG# 08-064-01-LIB and Women's Cancer Association Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 754. doi:10.1158/1538-7445.AM2011-754