Virotherapy
Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths.
[1] In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
[2] Oncolytic virotherapy is not a new idea – as early as the mid 1950s doctors were noticing that cancer patients who suffered a non-related viral infection, or who had been vaccinated recently, showed signs of improvement;[3] this has been largely attributed to the production of interferon and tumour necrosis factors in response to viral infection, but oncolytic viruses are being designed that selectively target and lyse only cancerous cells.
[5][6] It is believed that oncolytic virus achieve their goals by two mechanisms: selective killing of tumor cells as well as recruitment of host immune system.
[8] Tumor antigens and danger-associated molecular patterns are also released during the lysis process which helps recruit host immune cells.
[8] Currently, there are many viruses being used and tested, all differing in their ability to lyse cells, activate the immune system, and transfer genes.
[10] Oncolytic virotherapy as a monotherapy has also been tested in combination with other therapies including chemotherapy, radiotherapy, surgery, and immunotherapy.
The drug works by replicating in cancer cells, causing them to burst; it was also designed to stimulate an immune response but as of 2016, there was no evidence of this.
[17] The potential use of echovirus as an oncolytic virus to treat cancer was discovered by Latvian scientist Aina Muceniece in the 1960s and 1970s.
[19][20] On March 19, 2019, the manufacturer of ECHO-7, SIA LATIMA, announced the drug's removal from sale in Latvia, quoting financial and strategic reasons and insufficient profitability.
[8] Clinical trials include the tracking of viral replication and spread using various laboratory techniques in order to find the optimal treatment.
This leads to the idea that inhibiting the host's immune response may be necessary early in the treatment, but this is brought with safety concerns.
Due to these safety concerns of immunosuppression, clinical trials have excluded patients who are immunocompromised and have active viral infections.
[citation needed] Vectors made from Adeno-associated virus are one of the most established products used in clinical trials today.
Currently two therapies, Tisagenlecleucel and Axicabtagene ciloleucel are FDA-approved to treat acute lymphoblastic leukemia and diffuse large B-cell lymphoma respectively.
[24] In 2012 the European Commission approved Glybera, an AAV vector-based gene therapy product for the treatment of lipoprotein lipase deficiency in adults.
[citation needed] Vaccines are another method of virotherapy that use attenuated or inactivated viruses to develop immunity to disease.
[42][43] One such protozoa that potential virotherapy treatments have explored is Naegleria fowleri, which causes primary amebic meningoencephalitis (PAM).
However, virulent viruses of protozoal pathogens (VVPPs) can be used as viral therapies that can more easily access this eukaryotic disease organism by crossing the blood-brain barrier in a process analogous to bacteriophages.
[42] While these treatment methods for protozoal disease may show great promise in a manner similar to bacteriophage viral therapy, a notable hazard is the evolutionary consequence of using viruses capable of eukaryotic pathogenicity.
VVPP engineering must therefore control for viruses that may be able to mutate and thereby bind to surface proteins and manipulate the DNA of the infected host.
