Deep, Durable Response of Refractory Metastatic Synovial Sarcoma Following Vaccination for NY-ESO-1 using Dendritic Cell-Targeting Lentiviral Vector
Seth M. Pollack1,2, Hailing Lu3, Frank Hsu3, Jan ter Meulen3
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2University of Washington, Department of Medicine, Seattle, WA; 3: Immune Design, Seattle, WA
Synovial Sarcoma (SS) is a devastating cancer that can affect individuals of any age. Because it commonly expresses the cancer testis antigen NY-ESO-1 homogenously, it is an ideal disease for testing immunotherapeutic strategies that target this protein. LV305 is a dendritic cell-targeting, integration-deficient, lentiviral vector from the ZVex platform, which encodes the entire NY-ESO-1 protein. A patient with highly refractory, progressive SS was treated on a phase I trial of LV305. Elispot, flow cytometry and TCR Vβ repertoire sequencing were used to track T cell response following vaccination. The patient had mild fatigue and low-grade inflammatory type symptoms the day following her injections but had no grade 3 or higher toxicities related to treatment. She had a partial response with over 84.8% disease regression that is continuing at the time of this report, over 2 years post completion of the vaccination regimen with no additional anti-cancer therapies. A robust NY-ESO-1 specific CD4 and CD8 T-cell response formed following vaccination, which remains detectable. She has now returned to work, which she had not been able to do on her prior, cytotoxic therapies.
This is the first report of a cancer patient treated with a selectively dendritic-cell targeting lentiviral vector in vivo and any SS patient treated with NY-ESO-1 vaccination. A robust NY-ESO-1 specific CD4 and CD8 T-cell response formed following vaccination, which has been long-lasting and remains detectable at this time. LV305 is currently being evaluated in multiple phase 1 and phase 2 trials.