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Virotherapy is a treatment using biotechnology to convert viruses into cancer-fighting agents by reprogramming viruses to attack cancerous cells, while healthy cells remained relatively undamaged. Usually the viruses used are herpes simplex virus or Adenoviruses^{[citation needed]}.

It uses viruses as treatment against various diseases, most commonly as a vector used to specifically target cells and DNA in particular. It is not a new idea - as early as the 1950s doctors were noticing that cancer patients who suffered a non-related viral infection, or who had been vaccinated recently, showed signs of improvement^{[citation needed]}: 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.

In the 1940s and 1950s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors.^{[citation needed]} In 1956 some of the earliest human clinical trials with oncolytic viruses for the treatment of advanced-stage cervical cancer were started^{[citation needed]}. However, for several years research in this field was delayed due to the inadequate technology available. Research has now started to move forward more quickly in finding ways to use viruses therapeutically.

Specific projects and products[link]

RIGVIR - virotherapy preparation with antitumor activity, immune modulator

Since about 1965 scientists of the Institute of Microbiology in Latvia found antitumoral and immunomodulating capabilities of ECHO group enterovirus (RIGVIR). During more than 40 years of clinical trials, preparation of melanoma adopted ECHO-7 virus had shown promising results for melanoma patients. Virus Rigvir As of 2009^[update] is the only known viral preparation with immunoactivating and antitumor properties, which has passed all stages of clinical trials and is already introduced into the medical practice since 2004.^{[1][unreliable source?]}

RIGVIR belongs to the group of medicines called immune modulators. RIGVIR has antitumoral effect and is used in melanoma treatment, local therapy of melanoma skin and subcutaneous metastases, prevention of recurrences and metastases after a radical surgery. RIGVIR contains a live non-pathogenic virus of RNA type, which is not genetically modified. Due to its structurally functional formation RIGVIR selectively influences the cells of sensitive tumours, and causes specific immunity to itself thus activating the immune system cells. The active ingredient of RIGVIR is an ECHO group enterovirus which is non-pathogenic to people and does not cause immune suppression, which is, for example, the case with cold virus.

The direct antitumoral effect of RIGVIR refers to oncotropism and oncolysis.

The cytolytic function is selective - it refers only to malignant cells, without damaging healthy tissue cells. Very important is the fact that RIGVIR incites the expression of tumor-associated differentiation antigens on the surface of non-lysed malignant cells and suppresses the expression of MAGE group antigens which are associated with the progressive growth of melanoma. The altered surface structures of malignant cells turn into the target structures for cytotoxic mechanisms of the immune system.

The immune modulating effect of RIGVIR refers to the activation of lymph nodes, lymphoid tissues and immune cells. By inciting the immune reaction to itself, RIGVIR stimulates normal primary and secondary immunogenesis and cancels the local immunity block caused by the tumor. By activating immune reactions against the expressed tumor-associated antigens, the apoptosis-like process of immune rejection of the tumor takes place. The repeated application of the preparation in the course of efficiently managed virotherapy with RIGVIR enables to achieve gradual and complete regression of lymph node micro-metastases and subcutaneous metastases.

During the mentioned processes it is possible to trace how RIGVIR stimulates humoral immunity - the activation of B-cells, antibody production, induction of interferon simultaneously with activation of cellular, T-system immunity processes - in peripheral blood there is increase of cytotoxic CD8+-, helper CD4+-, and CD38+ cells. Also the cells of nonspecific immunity are activated: natural killers (NK) and macrophages are present. The function of lymph nodes are activated and lymphocyte infiltration into the tumor nidus increases, which indicated to the activation of local immunity processes.

It is convincingly proven that RIGVIR does not multiply in other human organs, tissue, and blood; and it does not excrete itself in the environment.

Undersirable side-effects of RIGVIR:

Like other medicines RIGVIR can cause side-effects which, however, do not show for all. The side-effects are temporary and do not require a special therapy.

The frequency of side-effects is defined in the following way: very often (≥1/10), often (≥1/100 to <1/10), less often (≥1/1000 to <1/100), rarely (≥1/10000 to <1/1000), very rarely (<1/10000).

RIGVIR is to be stored at the temperature -20°C±2°C and transported frozen.

In 2004, researchers from University of Texas have genetically programmed a type of common cold virus Adenovirus Delta-24-RGD to attack glioblastoma multiforme. Later other researchers ^[2] have tried tests on mice where 9 out of 10 mice have shown degeneration of tumors and prolonged survival. A drug grade virus has been approved for clinical trials on humans in 2009.^[3]

In 2006 researchers from the Hebrew University succeeded in isolating a variant of the Newcastle disease Virus (NDV-HUJ), which usually affects birds, in order to specifically target cancer cells.^[4] The researchers tested the new virotherapy on patients with glioblastoma multiforme and achieved promising results for the first time.

Vaccinia virus, a virus credited for the eradication of smallpox, is being developed as an oncolytic virus, e.g. GL-ONC1.^[5] Promising research results ^[6][7] warrant its clinical development in human patients.^[8]

The most advanced^{[citation needed]} virotherapy is that based on an engineered version of herpes simplex virus, known as OncoVEX GM-CSF, developed by BioVex. It is currently in Phase 3 clinical trials in melanoma and head and neck cancer^[9] having given a very high response rate^{[citation needed]} in previous trials in human patients.

See also[link]

• oncolytic virus
• virosome, using modified viruses for drug delivery
• Cancer
• Gene therapy
• Vector

References[link]