Cancer regression by induction of immunity to senescent cells 2627

Description Background Senescent cells contribute to tumor growth, immune suppression and resistance to therapy. We investigated anticancer efficacy of SenoVax™, a dendritic cell (DC) based senescent cell targeting immunotherapy. Materials and Methods SenoVax was prepared from syngeneic bone marrow derived DC pulsed with lysates of senescent fibroblasts in vitro. Fibroblasts were rendered senescent using doxorubicin and confirmed by expression of p16, beta-galactosidase, and HMGB1. Mice were implanted with 4T1 breast cancer, GL261 glioma, LLC lung carcinoma, PAN 02 pancreatic adenocarcinoma, and B16 melanoma cells and treated with SenoVax. Assessment of tumor growth and immunity was performed. Results and Discussion: SenoVax administration resulted in growth inhibition and regression of the 4T1, GL261, LLC, PAN 02, and B16 tumors in vivo. In vitro analysis of lymphocytes from SenoVax-treated mice demonstrated induction of immunity to senescence-associated p16 and p21 protein antigens. Tumor regressions were associated with immunological cell infiltration and reduction of the SASP protein IL-6 and augmentation of the natural killer cell-promoting cytokine IL-12. These data support filed IND 30745 representing a proposed clinical trial for SenoVax in lung cancer. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)