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Published on: November 24, 2014
Pre-existing Immunity to Oncolytic Virus Potentiates Its Immunotherapeutic Efficacy
Jacob M Ricca1, Anton Oseledchyk2, Tyler Walther1
1Department 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.
Abstract:
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.
Insights
Pre-existing anti-viral immunity to Newcastle Disease Virus (NDV) enhances its oncolytic virus (OV) therapy. Immunity improved tumor clearance and survival, suggesting potentiation of anti-tumor immunity.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Systemic administration of oncolytic viruses (OV) faces challenges from anti-viral immunity.
- Intratumoral OV therapy can activate anti-tumor immune responses, potentially overcoming systemic limitations.
- The impact of pre-existing anti-viral immunity on intratumoral OV efficacy remains unclear.
Purpose of the Study:
- To investigate the influence of pre-existing anti-viral immunity on the therapeutic efficacy of oncolytic viruses.
- To explore the effects of Newcastle Disease Virus (NDV) immunity on tumor treatment and anti-tumor immune responses.
Main Methods:
- Utilized syngeneic mouse tumor models to study oncolytic virus therapy.
- Employed Newcastle Disease Virus (NDV) as a model oncolytic virus.
- Assessed tumor clearance, abscopal anti-tumor immune effects, and survival in NDV-immunized and non-immunized mice.
Main Results:
- Pre-existing immunity to NDV restricted viral replication within tumors.
- Despite limited replication, NDV-immunized mice showed superior tumor clearance and improved survival.
- Abscopal anti-tumor immune effects were enhanced in mice with pre-existing NDV immunity.
Conclusions:
- Pre-existing anti-viral immunity to NDV can unexpectedly enhance its therapeutic efficacy as an oncolytic virus.
- This enhancement appears to be mediated by potentiation of systemic anti-tumor immunity.
- Findings support the clinical rationale for repeated dosing of NDV-based OVs and suggest similar effects may occur with other OVs.
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