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VSV-GP oncolytic virus

Targeting cancer with highly tumor-specific oncolytic viruses

VSV-GP oncolytic virus

Our VSV-GP oncolytic virus platform is an engineered oncolytic virus built upon VSV with a replaced surface glycoprotein, which acts by infecting and killing malignant cells and sparing their normal counterparts.1-4

Clinical trials: 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.5 Another first-in-human trial is evaluating BI 1821736 (VSV-GP oncolytic virus with immune-stimulatory cargo)* in patients with solid tumors.6

*This is an investigational compound and has not been approved. Its safety and efficacy have not been established.

Oncolytic Viruses

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 healthy, normal cells at the same time.1-4,7

About or VSV-GP oncolytic virus platform

The VSV-GP platform

Our VSV-GP oncolytic virus platform is an engineered oncolytic virus built upon VSV with a surface glycoprotein (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.3,8

Mechanism of action

The VSV-GP induces immunogenic cell death in tumors susceptible to type I interferon and stimulates immune cell recruitment into tumors (turning cold tumors into hot tumors).3,4 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

Gene cargos can be introduced into the viral genome. The local expression of gene cargos at the tumor site may enhance ​VSV-GP–mediated anti-tumor immune response.9

VSV-GP mechanism of action1-4

VSV-GO MoA

GP, glycoprotein; VSV, vesicular stomatitis virus.

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.3,4,10,11

Multiple studies have shown that oncolytic virus immunotherapy used in combination with other therapies have potential synergistic interactions and fewer additive adverse effects.1,2,6,12-18

Clinical development

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 was initiated in March 2022.5 Another first-in-human trial is evaluating BI 1821736 (VSV-GP oncolytic virus with immune-stimulatory cargo) in patients with solid tumors.6

VSV-GP oncolytic virus clinical trial

Trial numberPhaseTreatmentPatient populationStatus

NCT05155332 (1456-0001)5

I

BI 1831169 ± ezabenlimab (PD-1 inhibitor)

Solid tumors

Recruiting

NCT05839600 (1467-0001)6

I

BI 1821736

Solid tumors

Recruiting

 

FPI, first patient enrolled; GP, glycoprotein; VSV, vesicular stomatitis virus.

 

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  2. Kaufmann HL, et al. Nat Rev Drug Discov. 2015;14(9):642–662.

  3. Muik A, et al. Cancer Res. 2014;74:3567–3578.

  4. Tober R, et al. J Virol. 2014;88:4897–4907.

  5. ClinicalTrials.gov. NCT05155332. https://clinicaltrials.gov/study/NCT05155332. (Accessed: August 2023).

  6. ClinicalTrials.gov. NCT05839600. https://clinicaltrials.gov/study/NCT05839600. (Accessed: August 2023).

  7. Jhawar SR, et al. Front Oncol. 2017;7:202.

  8. Kimpel J et al. Viruses. 2018;10:108.

  9. Boehringer Ingelheim, data on file.

  10. Schreiber LM, et al. Br J Cancer. 2019;121:647–658.

  11. Mueller P, et al. Cancer Res. 2020;80(16 suppl):4450. 

  12. Marchini A, et al. Virol J. 2015;12:6.

  13. Russell SJ, et al. Nat Biotechnol. 2012;30(7):658–670.

  14. Maroun J, et al. Future Virol. 2017;12(4):193–213.

  15. Martin NT, Bell JC. Mol Ther. 2018;26(6):1414–1422.

  16. Hemminki O, et al. J Hematol Oncol. 2020;13(1):84.

  17. Khalil DN, et al. Nat Rev Clin Oncol. 2016;13(5):273–290.

  18. Kon T, et al. TCR. 2012;1(1):6–14.

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