Abstract 3543: Complete regression of solid B16F1 melanoma tumors obtained by intratumoral injection of LTX-315 (Oncopore®)

Abstract

Abstract Background: Malignant melanoma is imposing an increasing threat to the world's population and new therapies are needed.Standard treatment involves surgery, chemotherapy, and radiation therapy and often leads to relapse after ended therapy. LTX-315 (Oncopore®) is a chemically modified cationic cytolytic peptide which is equally active against drug-sensitive and drug-resistant cancer cells. Earlier animal studies have demonstrated that treatment of syngeneic murine A20 B-cell lymphomas and CT26WT colon carcinomas with intratumoral (i.t.) injection with LTX-315 resulted in complete tumor regression and long-term protective effect against re-inoculated tumor cells. The present study was undertaken to investigate whether LTX-315 induced an antitumor response in vivo in a highly aggressive murine melanoma tumor model. Methods: Pre-cultured B16F1 melanoma cells (5 x 104) were subcutaneously inoculated into the abdomen of syngeneic C57BL/6N mice and established tumors treated i.t. with LTX-315. Animals were taken for analysis to elaborate the mechanism of action of LTX-315 and for potential immune modulatory effects following treatment. Blood plasma was analyzed for changes in cytokine content and tumor tissue was analyzed for infiltrating immune cells using immunohistochemistry and flow-cytometry. Results: Intratumoral treatment with LTX-315 resulted in a complete regression of tumor in the treated animals. Tumors treated with LTX-315 showed an increased infiltration of immune cells into the tumor compared to control tumors receiving vehicle. Conclusions: Our results suggest that LTX-315 treatment can induce complete regression in solid B16F1 melanoma tumors, thus leading to local tumor control. Intratumoral treatment with LTX-315 can lead to immune-modulatory effects such as an increase in the number of infiltrating immune cells, causing a shift in the balance between immune effector and immune suppressive cells in the tumor environment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3543. doi:1538-7445.AM2012-3543