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April, 2017 >>

Oncolytic viral therapy

Syed Inam Ur Rehman, Syed Muhammad Haaris  ( 2nd Year Students, Dow University of Health Sciences, Karachi. )


Madam, this year; 1,685,210 people are expected to be diagnosed with cancer and about 595,690 people to die of it in USA alone.1 It's even more alarming that these figures are greater than the combined stats of diagnosed cancers and cancer related mortalities from 2008-2012.1 Conventionally cancers are treated using chemotherapy, radiation therapy and surgery which can impose devastating side-effects and recurrence is often seen.
In the early twentieth century the idea of the virus being a potential antineoplastic agent was being explored, after observing cases of short lived remissions in cancer patients following viral infections.2 It wasn't until late twentieth century that fundamental understanding of virus was established, thus it was from this point forward that research efforts in establishing Virotherapy gained momentum,2 which uses a genetically modified virus to treat cancers.
This therapy operates by two methods, lysis3 and by invoking immune responses.4 In the former, it preferentially invades the cancer cells and causes them to burst open, and then the latter tags in, releasing antigens which are presented to T cells5 which instigate an immune response. The outstanding characteristic of this therapy is its ability to target cancer stem cells which previous conventional therapies have failed to target.4,6 This treatment faces the challenge posed by the morpholocal and genetic hetergonecity that tumour cells flaunt, however using microarray technologies and proteomics, together with transcriptional targeting, its ability to preferentially target neoplastic cells and spare the normal ones.3
Lmlygic (uses Herpes Simplex Virus)7 is one such therapy which treats melanoma, approved by FDA. But one of the most impressive and bizarre examples is the role of polio virus against Glioblastoma8 which is currently being put through clinical trials in Duke University , but has shown positive results in stages as early as Phase 0. This also promises us a solution to cancers which have poor prognosis such as pancreatic adenocarcinoma.
Oncolytic therapy proposes a fundamental shift in cancer treatments, potentially changing the demographics of mortality due to cancers and its incidences and may ensure provision of a treatment that is safer and less terrifying. Thus it's a desperate domain of research which can help us uncover successful anti-neoplastic biotherapeutic agents and to understand it's mechanism of action to establish a well founded and effective system of research. Possible solutions are in the line, it is just the matter of effort of reeling it in.
Disclaimer: None to declare.
Conflict of Interest: None to declare.
Funding Disclosure: None to declare.


References

1. Cancer Statistics. [Online] [Cited August 2016] Available from: URL: http://www.cancer.gov/about-cancer/understanding/statistics.
2. Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther 2007; 15: 651-9.
3. Singh PK, Doley J, Kumar GR, Sahoo AP, Tiwari AK. Oncolytic viruses and their specific targeting to tumour cells. Indian J Med Res 2012; 136: 571-84.
4. Liu TC, Kirn D. Gene therapy progress and prospects cancer: oncolytic viruses. Gene Ther 2008; 15: 877-84.
5. Yu F, Wang X, Guo ZS, Bartlett DL, Gottschalk SM, Song XT. T-cell engager-armed oncolytic Vaccinia virus significantly enhances antitumor therapy. Mol Ther 2014; 22: 102-11.
6. Cripe TP, Wang PY, Marcato P, Mahller YY and Lee PWK. Targeting cancer-initiating cells with oncolytic viruses. Mol Ther 2009; 17: 1677-82.
7. Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol 2015; 33: 2780-8.
8. Gromeier M, Vlahovic G. Targeting cancer with genetically engineered poliovirus (PVS-RIPO). [Online] 2016 [Cited August 2016] Available from: URL: www.cancer.duke.edu/btc/ modules/Research3/index.php?id=41.


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