Abstract 641: Targeted inhibition of BRAF signaling in melanoma enhances the activity of a multivalent immunotherapeutic vaccine

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Development of a successful immunotherapeutic vaccine targeting melanoma requires the use of multiple melanoma associated antigens (MAA). Expression of several MAAs is regulated by the micropthalmia transcription factor (MITF), which in turn is regulated by members of the MAPK pathway, such as ERK. It is also known that 70% of melanomas express the genetic lesion BRAFV600E. Based on this knowledge, we hypothesize that the use of a specific BRAFV600E inhibitor would enhance MITF mediated MAA expression and thus serve as a viable target for immunotherapy. We have developed a vaccinia virus based melanoma vaccine using patient derived primary melanoma cells that are rich in MAAs such as gp100, tyrosinase, and TRP-1. Our results indicated that our cells were either homozygous or heterozygous for the mutated BRAF gene. In addition, our cells were responsive to treatment by PLX-4032, an FDA approved treatment for melanoma, as evidenced by inhibition of phosphorylation of MEK and ERK, two key players in the MAPK pathway. Phenotypically, the migratory and invasive properties of our cell lines were also altered by PLX-4032. Most interestingly was the observation that upon treatment with PLX-4032, the expression of various MAAs was altered. Specifically, the expression of gp100, MART-1, and tyrosinase increased both on the RNA level as well as on the protein level. Our results warrant further investigation into a combinatorial therapeutic approach to treat melanoma by which increasing the expression of various immunologically relevant MAAs, upon treatment with PLX-4032, followed by vaccination may lead to a more robust and targeted anti-melanoma immune response. Citation Format: Robert Suriano, Neha Tuli, Jan Geliebter, Raj K. Tiwari, Marc K. Wallack. Targeted inhibition of BRAF signaling in melanoma enhances the activity of a multivalent immunotherapeutic vaccine. [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 641. doi:10.1158/1538-7445.AM2014-641