Oncolytic virus immunotherapy utilizes native or genetically modified viruses to infect and lyse tumor cells, contributing to the induction of the systemic antitumor immune response and disruption of the tumor microenvironment.^1,2 

Most clinically relevant oncolytic viruses use naturally occurring viruses or attenuated strains with low pathogenic potential in healthy tissue.²

Once an oncolytic virus infects a tumor cell, it replicates and causes lytic cell death. This leads to the release of tumor-associated antigens, viral pathogen- and danger-associated molecular patterns, and cytokines, which together promote an efficient anti-tumor response. This increased response also alters the tumor microenvironment by decreasing immunosuppressive cells and changing neovasculature, preventing further tumor growth and spread.² 

Through genetic modification, the oncolytic virus can be used to target specific tumor types depending on characteristics such as selected surface receptors, aberrant signaling pathways, and the hypoxic tumor microenvironment with the advantage of sparing normal, healthy cells at the same time.^1–5

The first-in-human trial of our VSV-GP oncolytic virus (BI 1831169*) as a monotherapy and in combination with an anti–PD-1 inhibitor in patients with solid tumors is ongoing.⁶

VSV-GP oncolytic virus clinical trial

The VSV-GP platform

Our VSV-GP oncolytic virus platform is an engineered oncolytic virus built upon VSV with a surface GP replaced by the GP of the lymphocytic choriomeningitis virus.^3,4

This oncolytic virus was engineered to mitigate the risk of neurotoxicity and lower the risk of developing neutralizing antibodies, allowing repeated intra-tumoral and systemic administration.^3,4 As a cancer therapy, the VSV-GP oncolytic virus platform has many favorable characteristics—there is no evidence of genetic reassortment, malignant potential, or integration into the host genome, no history of pre-existing immunity in the general population, and it has a rapid, self-limiting replication cycle.^3,7

VSV-GP oncolytic virus mechanism of action

The VSV-GP induces immunogenic cell death in susceptible tumors deficient for interferon signaling and stimulates immune cell recruitment into tumors (turning cold tumors into hot tumors).^3,4,8 The oncolytic virus first enters a tumor cell and replicates rapidly, without integrating into the human genome. Tumor cell–specific antigens are then released via oncolysis, which, together with innate immune activation, induces anti-tumor activity. Viral progeny released from tumor cell death spreads to infect and replicate in other susceptible cells, repeating the same process.^1–4

VSV-GP oncolytic virus mechanism of action^1–4

Combination therapy

The VSV-GP has shown preclinical activity in a wide variety of solid cancer types, as well as synergy when combined with PD-1 blockade.^3,4,8,9

Multiple studies have shown that oncolytic virus immunotherapy used in combination with other therapies have potential synergistic interactions and fewer additive adverse effects.^{2,5,8,10−16}

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.
GP, glycoprotein; IFN, interferon; PD-1, programmed cell death protein-1; VSV-GP, vesicular stomatitis virus-glycoprotein.