Viruses are nature’s nanoparticles, a vast untapped bio-resource. Oncolytic viruses is a new class of anticancer drugs which have advantages of selective replication in tumor cells, delivery of multiple eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumor immunity. It is a tolerable safety therapy. Four oncolytic virus have been approved for the treatment of cancer globally. Talimogenelaherparepvec(T-VEC)istheonlywidelyusedtherapy.T-VECisused for treatmentofrecurrentmelanoma.[1] Oncolytic viruses are mutated such that they can be used as anticancer drugs in cancer therapy. They attack on selective tumor cells and destroy them without harming non-cancerous cells. With the help of virus-engineering strategies they are developed specifically for neoplastic tissues. Noninvasive pharmacokinetic monitoring is facilitated by engineering marker genes into the viral genome. [2] Oncolytic viruses are a class of therapeutic agents which give anti-tumor action by either selective tumor killing or induction of systemic anti-tumor immunity. Specific mutated viruses has been developed as oncolytic agents. Mechanism of action is likely dependent on viral replication within transformed cells, induction of primary cell death, interaction with tumor cell antiviral elements and initiation of innate and adaptive anti-tumor immunity. [3]We are going to see a brief review on the following topic in this article.
Introduction
Interest in using viruses to treat cancer began in the early 1900s after observations that viral infections could cause tumor regression. Early experiments with various viruses showed potential but had safety and consistency issues. Advances in genetic engineering from the 1970s onward enabled creation of modified viruses, such as Herpes Simplex Virus (HSV) mutants. This led to FDA approval of talimogenelaherparepvec (T-VEC) in 2015. Since then, multiple viruses like adenovirus, reovirus, and coxsackievirus have been explored, often combined with other cancer therapies.
Advantages:
Targeted cancer cell infection minimizing harm to healthy cells
Direct lysis of cancer cells
Activation of anti-tumor immune responses
Low toxicity and side effects
Potential for combination with other treatments
Tumor-specific replication amplifying effects
Systemic delivery to reach distant tumors
Customizable for personalized medicine
Disadvantages:
Possible development of viral resistance
Challenges in delivery and production scalability
Regulatory hurdles and public concerns about viral use
Risk of viral mutation causing unintended effects
Ideal Characteristics of Oncolytic Viruses:
Selective tumor targeting, high replication efficiency, strong immune activation, low toxicity, genetic stability, ability to target cancer stem cells, cost-effectiveness, and non-pathogenicity.
Mechanisms of Action:
Selective infection of cancer cells, immune system stimulation, direct cancer cell lysis, modulation of tumor microenvironment, induction of immunogenic cell death, and inhibition of tumor angiogenesis.
Future Directions:
Focus on combination therapies, personalized viral vectors tailored to patient genetics, and strategies to overcome viral resistance.
Types of Oncolytic Viruses:
Include engineered HSV, adenovirus, reovirus, vaccinia virus, Newcastle disease virus, measles virus, vesicular stomatitis virus, Maraba virus, Seneca Valley virus, and coxsackievirus.
Applications:
Used in oncolytic virotherapy, gene therapy, immunotherapy, targeted therapy, and treatment of solid tumors, lymphomas, pediatric cancers, and cancer stem cells.
Drug Selection Criteria:
Tumor specificity, oncolytic potency, immune stimulation, safety, delivery efficiency, genetic stability, scalability, synergy with other therapies, and regulatory approval.
Manufacturing & Evaluation:
Produced via cell culture and viral vector technologies, with rigorous quality control and safety testing through in vitro, in vivo, and clinical trials.
Clinical Results:
T-VEC and other oncolytic viruses have shown efficacy in melanoma and other cancers, with a generally favorable safety profile and promising results when combined with immunotherapies.
Marketed Products:
Examples include Imlygic (T-VEC), Oncorin (adenovirus), Reolysin (reovirus), Rigvir (picornavirus), Theravir (herpesvirus), Cavatak (coxsackievirus), and Vaxinia (poxvirus), used worldwide with variable costs and indications.
Conclusion
Utilizing certain viruses\' innate capacity to specifically infect and destroy cancer cells while inducing animmune response, mutated viruses as anticancer medications provide a novel approach to the treatment of cancer. Treatments that are more precise and efficient are coming from the continuous research in genetic engineering, combination therapy, and customized medicine. These treatments appear to have a good chance of becoming commonplace choices for cancer patients as long as clinical trials proceed. In summary, the future of mutated viruses in cancer therapy isbright,with ongoing advancements likely to yield significantbreakthroughs in the fight against cancer. [30]
References
[1] ShalhoutS.,MillerD.,EmerickK.,KaufmanH.(2023)Therapywithoncolyticviuses:progressand challenges [1]
[2] RussellS.,Pengk.(2007)Virusesasanticancerdrugs.Vol.28,issue-7 https://doi.org/10.1016%2Fj.tips.2007.05.005[2]
[3] KaufmanH.,KohlhappF.,ZlozaA.(2015)Oncolyticviruses:anewclassofimmunotherapydrugs[3]
[4] “Thehistoryofoncolyticvirotherapy”journalofclinicaloncology,2018[4]
[5] “Rabiesvirusvaccineinthetreatmentofcancer”cancerresearch,1951[5]
[6] “clinicaltrialsofviralcancertherapy”journalofthenationalcancerinstitute,1962[6]
[7] “Geneticengineeringofvirusesforcancertherapy”cancerresearch,1985[7]
[8] “Herpessimplexvirus-basedoncolyticviruses”journalofvirology,2001 [8]
[9] Kirnetal.(2001),ClinicalCancerResearh,7(10),3155-3163[9]
[10] Russelletal.(2012),NatRevCancer,12(9),658-668[10]
[11] Melcheretal.(2011),CancerRes,71(1),23-28[11]
[12] Vaha-koskelaetal.(2007),Molttherapy,15(6),1081-1088 [12]
[13] Kauretal.(2011),CancerResearch,71(11),3834-3841 [13]
[14] Paratoetal.(2012),Cancerresearch,72(10),2575-2584 [14]
[15] Poweretal.(2007),moleculartherapy,15(4),825-833 [15]
[16] Cattaneoetal.(2018),Cancerresearch,78(19),5381-5389 [16]
[17] https://www.google.com/gasearch?q=disadvantages%20of%20virus%20as%20anticancer%20drugs&tbm=
[18] #vhid=zephyr:0&vssid=atritem-[17]
[19] https://www.google.com/gasearch?q=ideal%20characteristics%20of%20virus%20as%20anticancer%20drugs&tbm=[18]
[20] Fillatetal.(2003),Cancergenetherapy,10(10),739-748 [19]
[21] Heinzerlingetal.(2011),Blood,118(19),5269-5278 [20]
[22] Wolleretal.(2018),Pediatricbloodcancer,60(3),373-378 [21]
[23] FDAGuidanceforindustry(2019),Oncolyticviraltherapy.[22]
[24] Andtbacka,R. H. I., et al. (2015). \"A Randomized, Open-Label Phase III Trial of TalimogeneLaherparepvec (T-VEC) in Patients with Unresectable Stage III Melanoma.\" Journal of Clinical Oncology, 33(25), 2780-2788.[23]
[25] Cohen, J. B., et al. (2015). \"OncoVEXGM-CSF in Patients with Advanced Melanoma: A Phase II Study.\" Clinical Cancer Research, 21(21), 4825-4833.[24]
[26] Gerritsen, W. R., et al. (2014). \"A Phase I Study of the Oncolytic Reovirus Reolysin in Combination with Carboplatin and Paclitaxel in Patients with Advanced Solid Tumors.\" Clinical Cancer Research, 20(22), 5723-5730.[25]
[27] Kottke, T. et al. (2016). \"Oncolytic viruses as a novel therapeutic approach for cancer.\" *Nature ReviewsClinical Oncology, 13(12), 787-802.[26]
[28] Friedman, R. (2018). \"Oncolytic viruses: A promising new approach for cancer therapy.\" Cancer Research, 78(12), 3035-3042. [27]
[29] Bommareddy, P. K. et al. (2018). \"Oncolytic viruses: A new frontier in cancer therapy.\" *Nature Reviews Drug Discovery, 17(12), 905-926.
[30] Zamarin,D.etal.(2021).\"Oncolyticvirustherapy:Aneweraincancertreatment.\"NatureReviews Cancer, 21(2), 115-129.
[31] Kumar,S.etal.(2022).\"Futuredirectionsinoncolyticvirotherapy:Acomprehensivereview.\"Cancer Gene Therapy, 29(3), 245-258.