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Hub AI
Virotherapy AI simulator
(@Virotherapy_simulator)
Hub AI
Virotherapy AI simulator
(@Virotherapy_simulator)
Virotherapy
Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
Chester M. Southam, a researcher at Memorial Sloan Kettering Cancer Center, pioneered the study of viruses as potential agents to treat cancer.
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; 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.[citation needed]
In the 1940s and 1950s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumours. In the 1940s–1950s some of the earliest human clinical trials with oncolytic viruses were started.
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. One of the major challenges in cancer treatment is finding treatments that target tumor cells while ignoring non-cancerous host cells. Viruses are chosen because they can target specific receptors expressed by cancer cells that allow for virus entry. One example of this is the targeting of CD46 on multiple myeloma cells by measles virus. The expression of these receptors are often increased in tumor cells. Viruses can also be engineered to target specific receptors on tumor cells as well. Once viruses have entered the tumor cell, the rapid growth and division of tumor cells as well as decreased ability of tumor cells to fight off viruses make them advantageous for viral replication compared to non-tumorous cells. The replication of viruses in tumor cells causes tumor cells to lyse killing them and also release signal to activate the host's own immune system, overcoming immunosuppression. This is done through the disruption of the microenvironment of the tumor cells that prevents recognition by host immune cells. Tumor antigens and danger-associated molecular patterns are also released during the lysis process which helps recruit host immune cells. Currently, there are many viruses being used and tested, all differing in their ability to lyse cells, activate the immune system, and transfer genes.[citation needed]
As of 2019, there are over 100 clinical trials looking at different viruses, cancers, doses, routes and administrations. Most of the work has been done on herpesvirus, adenovirus, and vaccinia virus, but other viruses include measles virus, coxsackievirus, polio virus, newcastle disease virus, and more. Methods of delivery tested include intratumoral, intravenous, intraperitoneal, and more. Types of tumor that are currently being study with oncolytic viruses include CNS tumors, renal cancer, head and neck cancer, ovarian cancer, and more. Oncolytic virotherapy as a monotherapy has also been tested in combination with other therapies including chemotherapy, radiotherapy, surgery, and immunotherapy.
In 2015 the FDA approved the marketing of talimogene laherparepvec, a genetically engineered herpes virus, to treat melanoma lesions that cannot be operated on; as of 2019, it is the only oncolytic virus approved for clinical use. It is injected directly into the lesion. As of 2016 there was no evidence that it extends the life of people with melanoma, or that it prevents metastasis. Two genes were removed from the virus – one that shuts down an individual cell's defenses, and another that helps the virus evade the immune system – and a gene for human GM-CSF was added. 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. The drug was created and initially developed by BioVex, Inc. and was continued by Amgen, which acquired BioVex in 2011. It was the first oncolytic virus approved in the West.
RIGVIR is a virotherapy drug that was approved by the State Agency of Medicines of the Republic of Latvia in 2004. It is wild type ECHO-7, a member of echovirus family. The potential use of echovirus as an oncolytic virus to treat cancer was discovered by Latvian scientist Aina Muceniece in the 1960s and 1970s. The data used to register the drug in Latvia is not sufficient to obtain approval to use it in the US, Europe, or Japan. As of 2017 there was no good evidence that RIGVIR is an effective cancer treatment. 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. However, several days later an investigative TV show revealed that State Agency of Medicines had run laboratory tests on the vials, and found that the amount of ECHO-7 virus is of a much smaller amount than claimed by the manufacturer. In March 2019, the distribution of ECHO-7 in Latvia has been stopped.
Virotherapy
Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
Chester M. Southam, a researcher at Memorial Sloan Kettering Cancer Center, pioneered the study of viruses as potential agents to treat cancer.
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; 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.[citation needed]
In the 1940s and 1950s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumours. In the 1940s–1950s some of the earliest human clinical trials with oncolytic viruses were started.
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. One of the major challenges in cancer treatment is finding treatments that target tumor cells while ignoring non-cancerous host cells. Viruses are chosen because they can target specific receptors expressed by cancer cells that allow for virus entry. One example of this is the targeting of CD46 on multiple myeloma cells by measles virus. The expression of these receptors are often increased in tumor cells. Viruses can also be engineered to target specific receptors on tumor cells as well. Once viruses have entered the tumor cell, the rapid growth and division of tumor cells as well as decreased ability of tumor cells to fight off viruses make them advantageous for viral replication compared to non-tumorous cells. The replication of viruses in tumor cells causes tumor cells to lyse killing them and also release signal to activate the host's own immune system, overcoming immunosuppression. This is done through the disruption of the microenvironment of the tumor cells that prevents recognition by host immune cells. Tumor antigens and danger-associated molecular patterns are also released during the lysis process which helps recruit host immune cells. Currently, there are many viruses being used and tested, all differing in their ability to lyse cells, activate the immune system, and transfer genes.[citation needed]
As of 2019, there are over 100 clinical trials looking at different viruses, cancers, doses, routes and administrations. Most of the work has been done on herpesvirus, adenovirus, and vaccinia virus, but other viruses include measles virus, coxsackievirus, polio virus, newcastle disease virus, and more. Methods of delivery tested include intratumoral, intravenous, intraperitoneal, and more. Types of tumor that are currently being study with oncolytic viruses include CNS tumors, renal cancer, head and neck cancer, ovarian cancer, and more. Oncolytic virotherapy as a monotherapy has also been tested in combination with other therapies including chemotherapy, radiotherapy, surgery, and immunotherapy.
In 2015 the FDA approved the marketing of talimogene laherparepvec, a genetically engineered herpes virus, to treat melanoma lesions that cannot be operated on; as of 2019, it is the only oncolytic virus approved for clinical use. It is injected directly into the lesion. As of 2016 there was no evidence that it extends the life of people with melanoma, or that it prevents metastasis. Two genes were removed from the virus – one that shuts down an individual cell's defenses, and another that helps the virus evade the immune system – and a gene for human GM-CSF was added. 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. The drug was created and initially developed by BioVex, Inc. and was continued by Amgen, which acquired BioVex in 2011. It was the first oncolytic virus approved in the West.
RIGVIR is a virotherapy drug that was approved by the State Agency of Medicines of the Republic of Latvia in 2004. It is wild type ECHO-7, a member of echovirus family. The potential use of echovirus as an oncolytic virus to treat cancer was discovered by Latvian scientist Aina Muceniece in the 1960s and 1970s. The data used to register the drug in Latvia is not sufficient to obtain approval to use it in the US, Europe, or Japan. As of 2017 there was no good evidence that RIGVIR is an effective cancer treatment. 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. However, several days later an investigative TV show revealed that State Agency of Medicines had run laboratory tests on the vials, and found that the amount of ECHO-7 virus is of a much smaller amount than claimed by the manufacturer. In March 2019, the distribution of ECHO-7 in Latvia has been stopped.
