Mam-A2.4 DNA vaccination leads to generation of effector phenotype CD8+ T cells and results in tumor regression. (131.1)

Abstract Mammaglobin-A (Mam-A) is a breast cancer-associated antigen expressed by approximately 80% of human breast tumors. Recently, seven epitopes derived from Mam-A were identified that bind HLA-A2 and are naturally presented by breast tumors, making these potential targets for immunotherapy. We show that epitope-specific, rather then full-length Mam-A DNA vaccination induces more effective tumor regression in vivo. Spleen cells from C57Bl/6 HLA-A2 mice, vaccinated with either full-length Mam-A DNA or epitope DNA (Mam-A2.1, Mam-A2.2, Mam-A2.4 and Mam-A2.6), were transferred into SCID-beige mice bearing tumors derived from the AU-565 (HLA-A2+/mammaglobin-A+) breast cancer cell line. Our results show that antigen-specific CD8+ T-cells derived from both full-length and epitope-specific DNA vaccination were initially capable of causing regression. However, only vaccination with Mam-A2.4 leads to long-term tumor regression, which can be further enhanced by low-dose total body irradiation of the tumor-bearing host. Furthermore, vaccination with Mam-A2.4 leads to the generation of CD8+ T-cells with an effector phenotype. These data demonstrate the potential of Mam-A single epitope DNA vaccination combined with low-dose total body irradiation as a therapy for the treatment and/or prevention of breast cancer.