LAUSR

Colorectal cancer (CRC) is the third most common cancer in the world, and approximately 50% of the patients develop liver metastasis, which is a major cause of disease mortality. New drugs and treatment options are therefore necessary to improve the survival of these patients. Lately, different types of immunotherapy, such as check point inhibitors, have shown great promise in the treatment of metastatic cancer, although for most patients with CRC the efficacy has been restricted to cases with microsatellite instable disease. Another novel immunotherapeutic strategy is oncolytic immunotherapy, which has been shown to cause immunogenic cancer cell death. Following cancer cell lysis, damage associated molecular patterns (DAMPs) are released, which are recognized by immune cell receptors. Pro-inflammatory responses will then be triggered to induce release of tumor specific antigens that are presented to the immune system, leading to tumor-specific immune responses. In the present study, we have investigated the efficacy of a novel oncolytic peptide, DTT-304, using two mouse models. Subcutaneous tumors were established in Balb c mice using the cell line CT26 and in C57Bl6 mice using the cell line MC38, both murine CRC cell lines. In both models, intra-tumoral injection of the peptide induced tumor necrosis and complete regression a few days after initiation of treatment, thus showing the potential of this peptide for use in colorectal cancer. In ongoing experiments we are investigating if the peptide has the potential to induce long lasting protective tumor-specific immune responses by re-challenging previously treated mice with the same cell line in a liver metastasis model. In addition, the possibility of treating liver tumors by direct peptide injection will be investigated. Citation Format: Karianne G. Fleten, Johannes J. Eksteen, Brynjar Mauseth, Ketil Camilio, Oystein Rekdal, Meng Yu Wang, Gunhild M. Maelandsmo, Kjersti Flatmark. The novel oncolytic peptide, DTT-304, induces regression of colorectal cancer tumors in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4705.