Via activation of the stimulator of interferon genes (STING) pathway, a new technology—AdVCA0848—may improve anti-tumor responses in patients with melanoma, according to researchers from Michigan State University (MSU), East Lansing, MI, who presented their results at the American Association for Cancer Research Annual Meeting 2017, in Washington, DC, in early April.
Researchers led by Andrea Amalfitano, PhD, DO, Osteopathic Heritage Foundation Endowed Professor of Pediatrics, Microbiology and Molecular Genetics at MSU, and Chris Waters, associate professor, Microbiology and Molecular Genetics, MSU, found that one intra-tumoral treatment with AdVCA0848 brought about the quick inhibition of tumor growth and improved survival compared with repeat doses of an anti-PD1 checkpoint inhibitor.
Compared with controls, a single intratumoral injection of AdVCA0848 significantly slowed B16 tumor growth (P < 0.01), which correlated with high levels of animal survival (P < 0.001). This significantly bested results achieved with the use of a PD-1 inhibitor. The combined use of AdVCA0848 treatment with anti-PD1 treatments further improved animal survival (50% survival at day 27 PTI) compared with the use of either AdVCA0848 or PD-1 treatment alone (36.4% and 26.7% survival at day 27 PTI).
Drs. Amalfitano and Waters also observed that AdVCA0848 generated high intracellular concentrations of STING agonists, sustained over days, which reduced the need for multiple treatments.
Previously, researchers had shown that AdVCA0848 causes the production of numerous inflammatory cytokines, which likely support anti-tumor responses and cause little systemic toxicity. Activation of the STING pathway delays tumor growth and promotes beneficial anti-tumor responses.
“This research begins to demonstrate that AdVCA0848 is both a safe and potent stimulator of the STING pathway, and this unique combination promotes safe induction of impressive anti-tumor responses in vivo,” concluded Dr. Amalfitano. “We are excited to further develop this novel immunotherapy and advance it rapidly to human clinical trials.”
This study was supported by Venn Therapeutics. This research is made possible in part through sponsored research and licensed technology partnerships with Michigan State University.