Spliceosomal Modulation Induces Immunogenicity of Melanoma Cells and In Vivo Immune Response

Spliceosomal Modulation Induces Immunogenicity of Melanoma Cells and In Vivo Immune Response

Alvin Sherman Library

Melanoma is an aggressive skin cancer with high mortality rates, often driven by BRAF and NRAS mutations. While targeted therapies like Vemurafenib have improved outcomes in BRAF-mutant melanoma, resistance and adverse effects limit their long-term efficacy. There is an urgent need for novel therapeutic approaches to overcome these challenges. This study investigates the efficacy of novel anti-melanoma compounds, 2155-14 and 2155-18, targeting spliceosomal proteins, in a xenograft model derived from the A375 BRAF/NRAS double mutant cell line. Seven-week-old mice were implanted with A375 BRAF/NRAS mutant cells and treated with 2155-14 or 2155-18. Treatments were administered subcutaneously thrice weekly. Tumor growth was measured using calipers, and tumor volume was calculated. Mice were monitored for clinical distress and sacrificed when tumors reached critical size. Tumor weights and volumes were analyzed statistically to determine treatment efficacy. Both compounds, 2155-14 and 2155-18, significantly reduced tumor volumes and weights compared to the vehicle control and the FDA-approved vemurafenib+cobimetinib treatment. The treatments did not adversely affect the body weights or overall health of the mice, indicating a favorable safety profile. The compounds 2155-14 and 2155-18 exhibit promising anti-melanoma activity in the A375 BRAF/NRAS xenograft model, suggesting their potential as therapeutic leads. Further studies are warranted to explore their safety and efficacy in preclinical and clinical settings, potentially offering a novel treatment avenue for melanoma patients resistant to current therapies.