Development of an immuno-competent mouse breast tumor model for pre-clinical evaluation of Mage-b2 DNA vaccine

R. Sypniewska, L. Hoflack, M. Tarango, C. Gravekamp

Research output: Contribution to journalArticlepeer-review

Abstract

Vaccine therapy is potentially less toxic than most of the currently used drug treatments and could be valuable for breast cancer patients. Tumor associated antigens (TAA) exclusively expressed on the cell membranes of tumors can activate anti-tumor cytotoxic T lymphocytes (CTL). The new generation of DNA vaccines uses cloned TAA to create tumor specific CTL. This novel approach need to be tested and optimized in animal models expressing the same or homologous TAA prior to clinical trial. For the development of such models, we analyzed mammary tumors for presence of TAA and identified the expression of Mage-b3 tumor antigens in transgenic MMTV-c-myc and MMTV-v-Ha-ras tumors. In addition we have identified another member of the Mage family, the Mage-b2, a homologue of human MAGE-B2 in Balb/c syngeneic mammary tumors. This model allows the induction of mammary tumors in immunocompetent Balb/c by injecting a mouse mammary tumor cell line 64pT cell derived from Balb/c mammary tumor. This mouse tumor model will be used to develop and to optimize Mage-b2 encoding DNA vaccines for breast cancer, and to test tumor immunological parameters in response to the vaccine. The complete protein encoding region of Mage-b2 has been cloned into an eukaryotic expression vector pCDNA3.1/V5-His-TOPO, and its identity was confirmed by Western Blotting. This vector has been used as a DNA vaccine in the syngeneic mouse model with mammary tumors expressing Mage-b2. Balb/c mice received Mage-b2 vaccine prior to challenge with 64pT tumor. In summary Mage-b2 (homologous to human MAGE-B2) has been identified for the first time in mouse mammary tumors. This is the first animal model that allows verification of the effect of the Mage-b2 vaccine in vivo (toxicity, tumor regression) and in vitro (Mage-b2-specific CTL responses). Current results indicate good tolerance of Mage-b2 vaccine and summary of anti-tumor responses will be presented.

Original languageEnglish (US)
Pages (from-to)310
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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