2025年5月30日
Oncolytic viruses in cancer treatment
Since the mid-1800s, there have been multiple cases of cancer patients experiencing tumor regressions that coincided with viral infections. The viral infections activated the patient’s immune system, which then attacked the cancer. This was an early type of immuno-oncology treatment.
Early clinical trials tested the viability of purposefully infecting cancer patients with a virus [3]. Indeed, many patients experienced tumor regressions, however, many also experienced undesirable side effects of said viral infection (ex: hepatitis). Patients needed a safer alternative infection with dangerous viruses. Today, oncolytic viruses are an emerging class of cancer therapeutics.
Historical observations of viral infections associated with tumor regression
1896 – A woman with “myelogenous leukemia” went into remission after influenza infection, 37 years before influenza was determined to be a viral infection [1]
1953 – Chicken pox led to regression of lymphatic leukemia in a 4-year-old boy [2]
Currently approved oncolytic viruses for clinical treatment
Oncorine (Shanghai Sunway Biotech) – approved by NMPA (China) in 2005 for nasopharyngeal carcinoma
Imlygic (Amgen) – approved by the FDA (USA) in 2015 for melanomas
Delytact (Daiichi Sankyo) – approved by Ministry of Health (Japan) in 2016 for glioblastomas
Antibody-based and cell therapies are still the dominant biotherapeutics for treating cancer. However, there is growing excitement around oncolytic viruses as mono- and combination therapies. A recent publication highlighted that the combination of intratumoral oncolytic virus (DNX-240) and a checkpoint PD1 inhibitor, pembrolizumab, “was safe with notable survival benefit in select patients.”[7] In June 2023, Oncolys announced preliminary data from a Phase II trial (NCT03921021) of its oncolytic virus treatment telomelysin combined with Merck’s Keytruda (pembrolizumab) in refractory gastroesophageal adenocarcinoma.
Certara’s experience with oncolytic viruses
To date, Certara scientists have worked on several oncolytic virus collaborations with such partners as OncoMyx. These collaborations helped predict whether the oncolytic virus will cause cytokine-mediated toxicity and the therapeutic and toxic effects of potential dosing schedules.
Using first principles, mechanistic models built at Certara can predict how uncertainties in virotherapy design lead to uncertainties in clinical efficacy/toxicity. Certara’s QSP software offers pre-built, validated model packs for gene therapy modalities allowing modelers and non-modelers to jumpstart their workflows.

Gene Therapy QSP Model Pack
Includes 8 models covering LNP-encapsulated mRNA and siRNA therapies
参照文献
[1] Dock G. The influence of complicating diseases upon leukaemia. The American Journal of the Medical Sciences (1827-1924). 1904 Apr 1;127(4):563.
[2] Bierman HR, Crile DM, Dod KS, Kelly KH, Petrakis NI, White LP, Shimkin MB. Remissions in leukemia of childhood following acute infectious disease. Staphylococcus and streptococcus, varicella, and feline panleukopenias. Cancer. 1953 May;6(3):591-605.
[3] Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Molecular therapy. 2007 Apr 1;15(4):651-9.
[4] Mondal M, Guo J, He P, Zhou D. Recent advances of oncolytic virus in cancer therapy. Human vaccines & immunotherapeutics. 2020 Oct 2;16(10):2389-402.
[5] Kaufman, H., Kohlhapp, F. & Zloza, A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 14, 642–662 (2015). https://doi.org/10.1038/nrd4663
[7] Nassiri, F., Patil, V., Yefet, L.S. et al. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial. Nat Med 29, 1370–1378 (2023). https://doi.org/10.1038/s41591-023-02347-y
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