Ricca et al. addressed the question of whether pre-existing antiviral immunity impacted the efficacy of intratumoral oncolytic virus therapy by first pre-establishing a systemic immune response against Newcastle Disease Virus (NDV) prior to tumor implantation and intratumoral virotherapy. Surprisingly, the efficacy of intratumoral oncolytic viral therapy increased in animals immune to NDV, leading to reduced Tregs and enhanced infiltration of distal tumors by conventional CD4+ and CD8+ T cells. CD8+ T cells, and to a lesser extent NK cells, were critical to this effect.
Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice. These findings demonstrate that pre-existing immunity to NDV may increase its therapeutic efficacy through potentiation of systemic anti-tumor immunity, which provides clinical rationale for repeated therapeutic dosing and prompts investigation of such effects with other OVs.
Author Info: (1) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Ce
Author Info: (1) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (2) Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (3) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (4) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (5) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (6) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (7) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. (8) Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Swim Across America-Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: zamarind@mskcc.org.
