Oncolytic viruses (OVs) are natural or recombinant attenuated versions of common viruses that do not cause disease, but which infect tumor cells preferentially over healthy cells. The virus eventually kills infected cells, which releases molecular and cell-derived fragments that stimulate an immune response against the remaining cancerous tissue.[i] This overall combined effect can occur with no prior knowledge of the cancer, its response to conventional treatments, or its specific antigenic composition.

Oncolytic viruses utilize a variety of viruses and vectors under current research and clinical trial – although limited commercial approvals exist to date.

According to GlobalData, over the last two years the number of global OV projects increased from 175 to 245. Most of the increase occurred at the preclinical stage where candidates increased from 66% to 76% of the overall number of candidates (Fig. 1).

Figure 1

The Leading OV Viruses

DNA viruses comprise 81.4% of all OVs studied thus far.[i] Of these, the leading OVs are adenovirus (41.9% of all OVs), herpes simplex virus (25.6%), and vaccinia virus (14%). RNA viruses account for 9.3% of development-stage OVs, led by coxsackie virus (4.7%), reovirus (2.3%) and poliovirus (2.3%). “Other” viruses account for 9.3% of studied OVs (Fig. 2).

figure 2

While all OVs infect and destroy tumors natively, they may be genetically modified for enhanced tumor infectivity, to deliver a genetic payload, or to improve the success rate of adjunctive therapies (e.g., immune checkpoint inhibitors).[i]  Through their ability to promote immune infiltration into infected tumors, OVs span the gap between direct tumor-killing and immunotherapy.[ii]

Adenoviruses are non-enveloped, double-stranded DNA organisms with high tropism for tissues in the eye, respiratory system, kidney, and lymphoid system.[iii] In addition to killing tumor cells directly, adenoviruses are highly immunogenic. Their recognition by specialized cellular receptors induces an immune response that initiates and supports the immune system component of OV activity.[iv]

The specificity of pox viruses for certain cancer cells is based on the unique combination of surface markers over-expressed on these cells.[v] The advantages of pox viruses as oncolytic agents is based on their safety, stability, relative ease of manufacturing at scale, and their amenability to genetic manipulation.[vi] Vaccinia virus, the most commonly used pox OV, is the basis of a live attenuated vaccine smallpox vaccine. As an OV, pox virus is under study for treating cancers of the liver, skin, lung, and for pediatric solid tumors.[vii]

Herpes simplex virus (HSV), another double-stranded DNA virus, has a comparatively large genome, only 20% of which is essential for infection and viral replication.[viii] This makes HSV an attractive candidate for genetic manipulation to enhance safety and tumor specificity. HSV is already quite safe for OV applications as it is not associated with mutagenesis, and responds well to antiviral treatment (as a safeguard against severe or disease-causing infection).[ix] HSV is under study for treating glioblastoma (among several neural cancers), sarcoma, and cancers of the breast, colon, liver, and thyroid.[x]

The Leading Cell Lines

Since stability/viability, scalability, and purification vary significantly among the twenty commonly used OVs, and even among the three leading vectors, some cell lines are more suitable for OV expression and expansion than others. Two lines, Vero and HEK293, stand out.

Vero cells are the leading expression host for producing viral vectors for both OVs and vaccines.[xi] Derived from monkey kidney epithelial cells, Vero cells possess defective innate antiviral defenses (they are interferon-deficient), which makes them particularly susceptible to infection. Many OVs are grown in Vero, including the three leading OVs plus rotavirus, reovirus, and Zika virus.

Derived from human embryonic kidney tissue, HEK293 cells are the leading human host cell line for OVs. HEK293 cells exhibit high transfectivity, rapid growth, and the potential for growth/expansion in serum-free suspension cultures that are easier to scale and purify.[xii] The U.S. Food and Drug Administration has approved seven biotherapeutics derived from HEK293 cultures, including several T cell-based cancer treatments. HEK293 is the leading expression host for oncolytic adenovirus and is also used to produce oncolytic reovirus.[xiii]

Despite intensive exploration into OVs only one has been approved by the U.S. Food and Drug Administration. Amgen’s T-VEC (Imlygic®), a modified HSV indicated in metastatic melanoma, infects and kills tumor cells and promotes an anti-tumor response through the release of antigenic tumor fragments and subsequent recruitment of tumor-killing immune cells.

Strategize Your Oncolytic Virus Production Plan with Us

Ongoing trials include products utilizing many viruses as both monotherapy and in combination with additional modalities to drive enhanced efficacy. This diversity of therapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for manufacturing. Thus, manufacturing production processes and regulatory approval paths need to be established for each OV individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species may require specific requirements for measures to ensure sterility. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability, are challenges common to several if not all OVs.

Our services support innovation in OVs through preclinical, clinical development and beyond (Table 1). We provide comprehensive services ranging from process development to GMP drug substance and drug product manufacturing, including aseptic processing capabilities. Our team of experts have a strong track record working with a variety of OV cell lines, including HEK293 and Vero, and with virus families that include adenovirus, poxviruses, and herpes simplex virus. We have a global network of facilities with extensive capabilities to develop both adherent- and suspension-based OV host cells from lab scale to commercial scale.


table 1


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[i]Russell, S.J., Bell, J.C., Engeland, C.E. et al. Advances in oncolytic virotherapy. Commun Med 2, 33 (2022). https://doi.org/10.1038/s43856-022-00098-4.

[ii] Li K, Zhao Y, Hu X, Jiao J, Wang W, Yao H. Advances in the clinical development of oncolytic viruses. Am J Transl Res. 2022;14(6):4192-4206. PMCID: PMC9274612.

[iii] Roberts MS, Groene WS, Lorence RM, Bamat MK. Naturally occurring viruses for the treatment of cancer. Discov Med. 2006 Dec;6(36):217-22. PMID: 17250786.

[iv] Aurelian L. Oncolytic viruses as immunotherapy: progress and remaining challenges. Onco Targets Ther. 2016 May 4;9:2627-37. doi: 10.2147/OTT.S63049. PMID: 27226725; PMCID: PMC4863691.

[v] Uusi-Kerttula H, Hulin-Curtis S, Davies J, Parker AL. Oncolytic Adenovirus: Strategies and Insights for Vector Design and Immuno-Oncolytic Applications. Viruses. 2015 Nov 24;7(11):6009-42. doi: 10.3390/v7112923. PMID: 26610547; PMCID: PMC4664994.

[vi] Shaw AR, Suzuki M. Immunology of Adenoviral Vectors in Cancer Therapy. Mol Ther Methods Clin Dev. 2019;15:418-429. Published 2019 Nov 13. doi:10.1016/j.omtm.2019.11.001.

[vii] Chan WM, McFadden G. Oncolytic Poxviruses. Annu Rev Virol. 2014;1(1):119-141. doi:10.1146/annurev-virology-031413-085442.

[viii] Smith GL, Moss B. Infectious poxvirus vectors have capacity for at least 25 000 base pairs of foreign DNA. Gene. 1983 Nov;25(1):21-8. doi: 10.1016/0378-1119(83)90163-4. PMID: 6229451.

[ix] Thorne SH. Next-generation oncolytic vaccinia vectors. Methods Mol Biol. 2012;797:205-15. doi: 10.1007/978-1-61779-340-0_14. PMID: 21948478.