Oncolytic Viruses in Bladder Cancer: Old Idea to Modern Approach

Editorial: Some viruses have the potential for tumor cell infection and killing. These viruses are known as oncolytic viruses. Oncolytic viruses can be found naturally or by genetic engineering to enhance cancer cell-killing potential with less harm to non-cancer cells. Research on virotherapy proposes that oncolytic viruses can also activate the immune system against the tumor. Until now, the only oncolytic virus with the US Food and Drug Administration (FDA) approval is genetically modified herpes simplex virus 1, talimogene laherparepvec (Imlygic®), or T-VEC for melanoma treatment. T-VEC is made by inserting two copies of the human cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) gene in its ICP34.5 loci, decreasing its pathogenicity while enhancing the recruitment of the immune cells in the tumor site (1).

It was in  1897 that  George Dock, a physician in Michigan, reported the first  Virus proposed as an effective treatment strategy for reducing leukemia in a woman after she had flu (2). Similarly, in 1971 a report of a child in Uganda with Burkitt’s lymphoma was bolded whose tumor went into remission after he contracted measles (3). In the 1990s, Canadian scientists recognized demolishing potential of infected cancer cells by common reovirus (4). After that, a virologist at Arizona State University in Tempe, Grant McFadden, reported that the rabbit virus could attack human cancer cells without damage to normal cells (5).

In 2019, Nicola E. Annels and colleagues from the UK showed that the common cold virus could infect bladder cancer (BC) cells. They represent a new way to treat non-muscle-invasive bladder cancer (NMIBC). CAVATAK (Coxsackievirus A21, CVA21) was administered to  15 BC patients a week earlier than transurethral resection of a bladder tumor (TURBT). Six patients received only the virus, while the other nine, in addition to the virus, got a dose of the chemotherapeutic agent )mitomycin C(. CAVATAK can increase the expression of ICAM-1 (Intercellular Adhesion Molecule 1) on tumor cells. ICAM-1 attaches to the CAVATAK and consequently expands its oncolytic activity. Finally, tumor demolition in all treated patients happened, and even one tumor disappeared (6).

Recently, Coby Rangsitratkul and colleagues indicated a noteworthy virus-mediated antitumor immunity of different oncolytic vesicular stomatitis virus (VSV) containing the human granulocyte-macrophage colony-stimulating factor transgene (VSVd51-hGM-CSF) in BC patient-derived organoids. They recommend that VSVd51-hGM-CSF can be a valuable policy in BC treatment (7). Numerous VSVd51 variants expressing GM-CSF have been formerly defined in several malignancies like melanoma and breast cancer (8, 9).  Coby Rangsitratkul and colleagues assessed equally the human and the existing mouse variant of VSVd51-mGM-CSF power to treat bladder cancer (BC). BC cell lines were assessed for vulnerability to viral lysis and expression of immunogenic cell death (ICD) markers and immune gene signatures. They examined the immunogenicity of VSVd51-mGMCSF in the C57Bl/6-MB49 syngeneic model to recognize these oncolytic viruses' fundamental in vivo immune system. In addition, on the BC patient-derived organoids, they check the immune system triggered by VSVd51-hGM-CSF.

Conclusion

Oncolytic viruses have been considered a gifted tool for straight-killing tumor cells. New research suggests that some oncolytic viruses can trigger an immune response in the body against cancer.

Authors’ contributions
All authors contributed equally.

Acknowledgments
None.

Conflict of interest
The author declares that there is no conflict of interest.

Funding
There is no funding.

Ethics statement
Not Applicable.

Data availability
None.

Abbreviations
BC            Bladder cancer
FDA          Food and Drug Administration
NMIBC     Non-muscle-invasive bladder cancer
VSV         Vesicular stomatitis virus