Follow-up of bi-shRNA furin / GM-CSF Engineered Autologous Tumor Cell (EATC) Immunotherapy Vigil® in patients with advanced melanoma

Minal Barve, Joseph Kuhn, Jeffrey Lamont, Peter Beitsch, Luisa Manning, Beena O. Pappen, Padmasini Kumar, Gladice Wallraven, Neil Senzer, John Nemunaitis
2016 Biomedical Genetics and Genomics  
Over the last decade, management of melanoma has dramatically evolved from chemotherapy through targeted molecular therapy (BRAF V600E signaling) and, currently, immunotherapy (checkpoint inhibitors, immunogenic oncolytic viruses). Response, time to progression and survival has improved for many melanoma patients undergoing targeted therapy, but insensitive population subsets, adaptive resistance and toxic side effectslimit therapeutic benefit. Previous studies have shown a correlation between
more » ... igil  engineered autologous tumor cell (EATC) immunotherapy induced circulating activated T-cells responsive against autologous tumor cells and survival prolongation. We now assess the safety and response to Vigil (1 x 10 7 cells/ intradermal injection monthly x 4-12 months) in 12 patients with advanced metastatic melanoma in comparison with 12 who underwent similar standard of careautologous tumor harvest but received other treatment regimens rather than Vigil. None of the patients experienced≥ Grade 3 treatment-related toxicity. Two Grade 2 adverse events (AE) (fatigue, irritability) and local regionalGrade 1 AE (injection site erythema, induration, rash, skin hypopigmentation)in 19 of 63 injections were observed. IFN-γ ELISPOT analysis (PBMC) showed the induction ofT-cell activation from 0-1 at baseline to 78 spots/10 6 cells post first cycle of Vigil. Median survival of Vigil treated patients was 20 months compared to 7 months (KaplanMeier analysis, log rank p=0.00009). In conclusion, preliminary evidence of safety and activity of Vigil supportsfurther clinical evaluation in advanced melanoma.
doi:10.15761/bgg.1000116 fatcat:xd3wsb6t4ne6zcytcd7car5fge