Abstract 2584: Complete regression and protective immune responses obtained in B16 melanomas after treatment with LTX-315 (Oncopore®)

Abstract

Abstract Background: Malignant melanoma is the most aggressive and deadliest form of skin cancer, with a high mortality rate among late-stage melanoma patients. This calls for new and improved therapies within the field. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line of defense against pathogens, and several CAPs have shown promising anticancer activity. Structure-activity relationship studies on the CAP bovine lactoferricin has resulted in the design of a short chemically modified lytic anticancer peptide, LTX-315, which has potential as a new anticancer drug. Previous animal studies conducted with LTX-315 have demonstrated that intratumoral (i.t.) treatment of syngeneic murine A20 B-cell lymphomas and CT26WT colon carcinomas resulted in complete tumor regression. In the present study, we investigated the antitumor effects of LTX-315 against highly aggressive B16 melanomas in syngeneic mice. Methods: The cytotoxicity of LTX-315 was tested against a series of cell lines in vitro using the MTT assay. B16F1 melanoma cells (5 x 104) were intradermally inoculated into the abdomen of syngeneic C57BL/6N mice and established tumors treated i.t. with LTX-315. Tumor tissue and blood samples were taken for analysis to elaborate the mechanism of action of LTX-315 and for potential immune modulatory effects following i.t. treatment. Blood plasma was analyzed for IL 1β and IL 6 content and tumor tissue was analyzed for infiltrating immune cells and expression of pro-inflammatory cytokines using immunohistochemistry and real time qPCR, respectively. Results: LTX-315 rapidly kills B16 melanoma cells and induces the release of Danger-Associated Molecular Pattern molecules such as the High Mobility Group Box-1 protein in vitro. Intratumoral (i.t.) administration of LTX-315 resulted in tumor necrosis and the infiltration of immune cells into the tumor parenchyma followed by a complete regression of the tumor in the majority of the animals. Animals cured by LTX-315 treatment were protected against a re-challenge with live B16 tumor cells. Conclusions: Our results demonstrate that LTX-315 i.t. treatments with LTX-315 induces complete regression of solid B16F1 melanoma tumors, thus leading to local tumor control, followed by protective immune responses. Thus, LTX-315 has potential as a novel immunotherapeutic agent. Citation Format: Ketil André Camilio, Gerd Berge, Chandra Sekhar Ravuri, Øystein Rekdal, Baldur Sveinbjørnsson. Complete regression and protective immune responses obtained in B16 melanomas after treatment with LTX-315 (Oncopore®). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2584. doi:10.1158/1538-7445.AM2014-2584