Abstract 5012: Establishment of a transplantable, NY-BR-1 expressing breast cancer model in HLA-transgenic mice

Abstract

Abstract Introduction: Breast cancer is one of the leading causes of cancer related deaths in women worldwide and current standard therapies show limited efficacy. However, immunotherapeutic approaches like adoptive T cell transfer might represent an attractive option for the treatment of breast carcinoma. The differentiation antigen NY-BR-1 appears as a suitable target for T cell immunotherapy against breast cancer as it is overexpressed in 60% of breast carcinomas compared to healthy breast. Objectives: The aim of this project is to establish a NY-BR-1-expressing, transplantable tumor model in HLA transgenic mice that would allow to investigate the functional role of NY-BR-1-specific HLA-restricted CD4+ T cells in vivo with respect to their capacity to sustain cytotoxic T lymphocytes (CTL)-mediated tumor attack. Furthermore, the capability of NY-BR-1-specific CD4+ T cells to interact with tumor-associated macrophages (TAMs) thereby potentially promoting differentiation of TAMs into immunostimulatory type-1 macrophages (M1) will be investigated. Materials and methods: Stable transfectant clones of the C57BL/6 derived lymphoma cell line EL4 and of the mammary adenocarcinoma cell line EO771 expressing NY-BR-1 were established. Furthermore, an H2Db-restricted, NY-BR-1-specific CTL epitope could be identified which upon peptide immunization of C57BL/6 mice resulted in the generation of NY-BR-1 specific, H2Db-restricted CTL lines, similarly to immunization with a rec. NY-BR-1 encoding adenovirus as observed in parallel experiments. Results and conclusions: Transplanted EL4 and EO771 derived transfectant clones stably expressing NY-BR-1 gave rise to subcutaneous tumors in H2-compatible, HLA-DR4 transgenic mice. In addition, a NY-BR-1-specific CTL line recognizing EL-4/NY-BR-1 expressing transfectants in vitro was successfully generated upon peptide immunization as described above. Studies to investigate the cooperative effect between the aforementioned CTL line and HLA-DR3- and HLA-DR4-restricted NY-BR-1-specifc CD4+ T cell lines, upon joint adoptive transfer into tumor bearing HLA-transgenic mice are currently ongoing. The results presented here demonstrate the first NY-BR-1 expressing mouse tumor model, allowing the investigation of NY-BR-1-specific immune responses in vivo. Citation Format: Krishna Das, Adriane Gardyan, Mathias Vormehr, Karin Mueller-Decker, Inka Zörnig, Dirk Jäger, Wolfram Osen, Stefan B. Eichmüller. Establishment of a transplantable, NY-BR-1 expressing breast cancer model in HLA-transgenic mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5012. doi:10.1158/1538-7445.AM2015-5012