Cancer immunotherapy: treatment of established breast cancer or prevention of tumor relapse and metastasis? (TUM2P.903)

Abstract

Abstract Cancer vaccines and adoptive immunotherapies (AITs) are being tested both in preventive and therapeutic settings. In order to determine the most effective immunotherapeutic strategy, we investigated the efficacy of AIT against established advanced carcinoma and minimal residual disease. We used Decitabine to improve immunogenicity of the tumor cells by inducing the expression of cancer testis antigens (CTA), in vivo. Tumor-sensitized immune cells were activated and reprogrammed, ex vivo, using bryostatin 1 and ionomycin, along with IL-2, IL-7, and IL-15; this produced a central memory phenotype in 73% of T cells, and an activated phenotype in 27% of NK cells and 94% of NKT cells. FVBN202 transgenic mice were protected from developing lung metastases following AIT, but failed to cure established lung metastases. The reprogrammed immune cells also demonstrated immunological memory that protected animals from recall tumor challenge. In vitro studies showed that reprogrammed immune cells were able to kill 82% of viable Adriamycin-treated quiescent tumor cells. Our results suggest that AIT could be efficacious against chemotherapy-resistant dormant tumor cells in a setting of low tumor burden and prevent distant metastasis of breast cancer. These findings are significant because breast cancer mortality results from metastatic disease that develops from residual tumor cells remaining dormant, sometimes for prolonged periods following conventional therapies.