Abstract Approximately 50% of human melanoma is driven by B-Raf protooncogene mutation (BRAF-mutant). Tumors with such mutation are highly immunosuppressive, and often resistant to immune checkpoint inhibitor (ICI) therapies. Blocking the BRAF-MAPK pathway in the BRAF-mutant melanoma cells markedly increases the tumor antigen expression and hence enhances the ability of T cells to recognize autologous BRAFV600 mutant melanoma cells. In parallel, induction of immunogenic cell death (ICD) of melanoma cells can overcome immunosuppression and enhance the antigen presenting capacity of dendritic cells (DCs). Therefore, our goal is to engineer a novel nanomedicine for combined delivery of BRAF inhibitor and ICD inducer drugs for immunogenic eradication of melanoma cells and thus boost the efficacy of ICI therapy. First, we engineered liposomes encapsulating dabrafenib (DFN, BRAF inhibitor) and selumetinib (SLM, MEK inhibitor). To ensure their stability, we coupled DFN and SLM to cholesterol via pH-responsive carbamate and ester bonds, respectively prior to incorporation into liposomes. The liposomes showed uniform size, high drug loading and excellent physical stability as well as high internalization and cytotoxicity against A375 melanoma cells. Moreover, the expression of MHC I Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6397.
Ziada et al. (Fri,) studied this question.