Abstract 477: Long-term protection against B16F1 melanoma upon vaccination with tumor cell lysate combined with LTX-315 as a novel adjuvant.

Abstract

Abstract Here, we demonstrate the potency of LTX-315 as a novel adjuvant in combination with B16F1 tumor cell lysate vaccine. LTX-315 is a chemically modified cationic peptide derived from a family of molecules called host defense peptides. Through its cytolytic activity, the main mechanism of LTX-315 is the induction of immunogenic cell death which leads to local inflammation by recruitment and activation of the immune system at the injection site. This is important to obtain strong vaccine-specific immune responses. We have selected the B16F1 melanoma model for this study since this tumor model is poorly immunogenic and have been described for being notoriously difficult to treat. Mice were vaccinated once a week for 4 weeks and challenged with viable B16F1 cells s.c. two weeks after the last vaccination. Tumor protected mice were re-challenged 10 weeks post primary challenge. In contrast to other studies where tumor growth inhibition is observed for this model, our results not only demonstrate complete tumor regression, but also long-term protection against the B16F1 melanoma. In total, 14/18 animals had established long-term protection which indicates induction of immunological memory against B16F1 melanoma. In conclusion, LTX-315 is a novel adjuvant with substantial potency to induce strong and durable immune responses against the poorly immunogenic B16F1 in vivo. The efficacy of vaccinations to further document the potency of LTX-315 as an adjuvant are currently studied in therapeutic and metastatic B16 models and other orthotopic models. The present results indicate the potential of LTX-315 to be a next generation adjuvant for therapeutic vaccines based on tumor-associated antigens (TAA). Citation Format: Gerd Berge, Ketil Andre Camilio, Øystein Rekdal, Ali Areffard. Long-term protection against B16F1 melanoma upon vaccination with tumor cell lysate combined with LTX-315 as a novel adjuvant. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 477. doi:10.1158/1538-7445.AM2013-477