Immunotherapeutic Cell-Based Vaccine to Combat Metastatic Breast Cancer

摘要

Because metastases spread to many different organs and few animal models accurately reflect the clinical progression of metastatic disease, it has been difficult to develop effective therapies to specifically target these lesions. We analyzed the poorly immunogenic mouse 4T1 mammary carcinoma and demonstrated that it is an excellent model for human metastatic breast cancer. Primary 4T1 tumors displayed signs of edema, extension to the peritoneal lining, and ulcerations of the skin, which are acute diagnostic indicators of human stage IV breast cancer. More importantly, the frequency and sites of metastasis were highly comparable between 4T1 and its human counterpart. In a post- operative system, where primary 4T1 tumor is surgically removed and survival is monitored, we showed that early metastases responsible for morbidity are established by 2 weeks and that survival of these mice extends a total of 5-7 weeks. We tested novel cell-based vaccines combining MHC class II, B7.l, SEB superantigen, and IL-12 in varying protocols where wildtype spontaneous metastases were pre-established ranging from 2-4 weeks.