Novel immunotherapeutic approaches to fight metastatic breast cancer

Absttract

Breast cancer is the second most common cancer in women. Breast cancer patients have a reasonable chance of becoming cured, particularly when they are diagnosed in an early phase. Eliminating primary tumors by surgery, chemotherapy, or radiation is quite successful. However, for metastases there is no cure. Thirty percent of the breast cancer cases will progress into metastatic disease, but they cannot be removed by surgery or radiation, and usually become chemoresistant. However, preclinical and clinical studies have shown that cancer vaccination has an effect on metastases but that a real breakthrough is hampered by the strong immune suppression in the tumor microenvironment (TME). Therefore, in this thesis we focused on the treatment of metastatic breast cancer using an attenuated Listeria monocytogenes (Listeriaat)-based vaccine expressing tumor-associated antigen (TAA) Mage-b, combined with adjuvants such as Curcumin or alphagalactosylceramide (!GC), to reduce immune suppression in the TME in order to improve the vaccine efficacy of Listeriaat-Mage-b.