Virotherapy
Encyclopedia
Virotherapy is a treatment using biotechnology
to convert virus
es 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.
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: 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 tumor
s. In 1956 some of the earliest human clinical trials with oncolytic viruses for the treatment of advanced-stage cervical cancer
were started. 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.
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 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.
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 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.
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. 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. Promising research results warrant its clinical development in human patients.
The most advanced 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
having given a very high response rate in previous trials in human patients.
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
to convert virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es 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.
It uses viruses as treatment against various diseases, most commonly as a vector used to specifically target cells and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
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: this has been largely attributed to the production of interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
and tumour necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
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 tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s. In 1956 some of the earliest human clinical trials with oncolytic viruses for the treatment of advanced-stage cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
were started. 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
RIGVIR - virotherapy preparation with antitumor activity, immune modulatorSince about 1965 scientists of the Institute of Microbiology in Latvia found antitumoral and immunomodulating capabilities of ECHO group enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
(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 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.
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).
| System of organism | Very often | Often | Less often | Rarely | Very rarely |
|---|---|---|---|---|---|
| General disorders | Temperature to 37,5°C, temporary (1–3 days) | Pains in the tumor region, fatigue | |||
| Nervous system disorders | Drowsiness | ||||
| Stomach-intestinal canal function disorders | Dyspepsia (diarrhoea) | ||||
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
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
virus Adenovirus Delta-24-RGD to attack glioblastoma multiforme. Later other researchers 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.
In 2006 researchers from the Hebrew University succeeded in isolating a variant of the Newcastle disease
Newcastle disease
Newcastle disease is a contagious bird disease affecting many domestic and wild avian species. First found in Newcastle, United Kingdom in 1926, then by Burnet in 1943 in Australia in connection with laboratory infection where the virus was isolated from a ocular discharge of a patient to show the...
Virus (NDV-HUJ), which usually affects birds, in order to specifically target cancer cells. The researchers tested the new virotherapy on patients with glioblastoma multiforme
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...
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
Oncolytic virus
An oncolytic virus is a virus that preferentially infects and lyses cancer cells; these have obvious functions for cancer therapy, both by direct destruction of the tumour cells, and, if modified, as vectors enabling genes expressing anticancer proteins to be delivered specifically to the tumor...
, e.g. GL-ONC1. Promising research results warrant its clinical development in human patients.
The most advanced virotherapy is that based on an engineered version of herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
, known as OncoVEX GM-CSF, developed by BioVex. It is currently in Phase 3 clinical trials in melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
and head and neck cancer
Head and neck cancer
Head and neck cancer refers to a group of biologically similar cancers that start in the upper aerodigestive tract, including the lip, oral cavity , nasal cavity , paranasal sinuses, pharynx, and larynx. 90% of head and neck cancers are squamous cell carcinomas , originating from the mucosal lining...
having given a very high response rate in previous trials in human patients.
See also
- oncolytic virusOncolytic virusAn oncolytic virus is a virus that preferentially infects and lyses cancer cells; these have obvious functions for cancer therapy, both by direct destruction of the tumour cells, and, if modified, as vectors enabling genes expressing anticancer proteins to be delivered specifically to the tumor...
- virosomeVirosomeA virosome is a drug or vaccine delivery mechanism consisting of unilamellar phospholipid bilayer vesicle incorporating virus derived proteins to allow the virosomes to fuse with target cells...
, using modified viruses for drug delivery - CancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
- Gene therapyGene therapyGene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
- Vector