Vaccine for prevention of breast cancer
2580 Background: Women with high risk breast cancer still succumb to their disease despite existing programs of adjuvant therapy. Thus, new approaches for adjuvant therapy are needed. Her-2-Neu overexpression on a breast cancer cells correlates with recurrence, metastasis and resistance to chemotherapy and radiation therapy. The immune response is tolerant of tumor associated antigens (TAA) like Her-2-Neu since they have been present on epithelial cells since birth. The immune response to vaccines in women with breast cancer is limited by the diminished number of CD4 and CD8 T cells and qualitative defects of CD4 cells in individuals above the age of 50. Methods: The following strains of mice were vaccinated: 6–8 week old hMUC-1.Tg mice, and rH2N.Tg mice, as well as 18 month and 2 month old C57BL/6J mice, by injecting subcutaneously the Ad-sig-TAA/ecdCD40L vector prime followed by sc injections of the TAA/ecdCD40L protein boost. Results: Vaccination of 18 month old mice with the Ad-sig-TAA/ecdCD40L vector prime protein boost produce regressions of TAA positive sc tumor and a 5 fold increase in antigen specific spleen cells, a 10X increase in subcutaneous tumor nodules of antigen specific effector CD8 T cells by tetramers, and a 2X decrease of CD4+CD25+FOXP3+ cells. Vaccination of rH2N.Tg mice starting at 6 weeks with the Ad-sig-rH2N/ecdCD40L vector prime/protein boost prevented the development of breast cancer in 50% of the mice. The Ad-sig-hMUC-1/ecdCD40L vector prime/ hMUC-1/ecdCD40L protein boost induced hMUC-1 specific antibodies in hMUC-1.Tg mice which bound to human breast cancer specimens. The rH2N/ecdCD40L vector prime/protein boost vaccine suppressed growth of rH2N positive tumor cells and this effect was potentiated by concomitant administration of chemotherapy. Conclusions: These results suggest that the Ad-sig-TAA/ecdCD40L platform can be used to suppress the growth of existing breast cancer even in old mice and prevent the development of breast cancer. We are preparing a phase I clinical trial of this approach in the setting of breast cancer patients who have failed first line adjuvant therapy. In this trial, the vaccine will be added to established salvage therapy and both in vivo evaluations of tumor response, in vitro assays of immune response and toxicity will be measured. No significant financial relationships to disclose.