Latvian Virotherapy Center
The studies on usage of viruses in therapy of malignant tumours are intensively taking place all over the world, scientists in different countries around the world are increasingly accepting virotherapy as the most promising cure for many types of cancer.
Virus Rigvir, a result of discoveries, made by Latvian scientists, and achievements of immunologists and oncologists, today is the only known viral preparation with immunoactivating and antitumour properties, which has passed all stages of clinical trials and is already introduced into the medical practice. To support and promote virotherapy as science and very promising practical medicine in October 2008 Latvian scientists, immunologists and oncologists established Latvian Virotherapy Center.
Virotherapy center tasks and future goals:
- Promotion of the development of virotherapy as practical medicine and a promising and perspective science
- Organization of trainings in practical virotherapy and assessment of immune status
- The implementation of medical consultations
- Support of scientific research, scientific publishing
- Hosting and participation in international scientific conferences in Latvia and abroad
Virotherapy
The biotherapy is a kind of therapy which, by means of the preparations of natural origin mobilizes the innate antigen specific adaptive immune cells and system against foreign genetical information, genetically modified cells and tissue of the organism including malignant cells.
Since 1980-s in oncological science has been established conviction, that the immune defense against the tumour fails not due to the lack of surface antigens in the tumour, but due to the fact, that the tumour successfully avoids immune control and inhibits/blocks all immune reactions targeted to the tumour.
Modern oncology is using the protective activities of the immune mechanisms, promotors of stabilization and preparations to change the surface structures of the tumour cells and make them visible target to the natural immune defense. Such properties are possessed by oncotropic viruses and cytokines, including interferons.
The application of oncotropic/oncolytic viruses in oncology is called virotherapy and it is a kind of biotherapy.
Virotherapy in the tissue susceptible to the respective virus like radio- and chemotherapy causes cell death (cytolysis). In comparison with chemotherapy and radiotherapy virotherapy has several advantages:
- Very high therapeutical index, sometimes even 10000:1 (10.000 tumour cells are killed against 1 normal cell).
- More rapid elimination of virotherapy caused cell destruction products (in case of radio- and chemotherapy elimination is protracted due to immunosuppression caused by these therapies).
- The combination of virotherapy and chemotherapy increases the antitumoral effect. This conclusion made in Latvia in1972, has been proved in experimental and clinical investigations of Australian and Canadian virotherapeutists in 1990.
- In the susceptible tumours virotherapy due to the oncotropism, i.e. induced by the viral infection of cancer cell, modifies the surface structures of cancer cell, thus submitting just these cells to specific cytotoxic immune mechanisms.
Therefore virotherapy is also the method for the activation of antigen-specific mechanisms of immune protection.
The best results were achieved in the early stages of the tumour, using biotherapy after surgery for the prevention of metastases. Biothrerapy is not a silver bullet, good results can not be promised in the late stages of cancer, when all possible treatments have been exhausted.
Application of virotherapy treatment shall be local and systemic. Virotherapy can be combined with other methods used in oncology, such as surgery, radiotherapy, chemotherapy and hormonal therapy. In such combinations the suppression of immunity (the effect of immunosuppression) is reduced due to the above methods of treatment effect. Virotherapy currently is probably the only option to cure tumours, which are not sensitive to radiotherapy and chemotherapy (melanoma, hipernefroma, etc.).
The effect of virotherapy to a higher extent depends on the condition of patient’s immune system as well as progression of cancer process before the treatment. During virotherapy course, which could last several years, it is highly recommended to monitor patient's immune status and consult immunologist.
Guidelines for the practical application of virotherapy have been developed by Latvian scientists and practicing immunologists,led by Professor Aina Muceniece. These guidelines, according to the principle of regional administration, and depending on tumour progression and patient's immune system status, recommend frequency and duration of virotherapy course, as well as the virus injection site to reach the higher therapeutic effect.
World experience:
http://www.isracast.com/tech_news/260106_tech.aspx
http://www.bioline.org.br/request?mj03002
http://discoverysedge.mayo.edu/measles/
http://www.mayoclinic.org/news2007-rst/3954.html
http://www.collegiatetimes.com/news/1/ARTICLE/8949/2007-04-12.html
http://www.epeiusbiotech.com
You may acquaint yourself with the information of Rigvir only if you are health care professional!!!
Virus RIGVIR
Virotherapeutical preparation with antitumoral activity, immunomodulator with philogenetically determined pleiotropic specific and nonspecific immunemodulating activities. Due to the structural functional formation selectively affects cells of susceptible tumour and inducing specific immunity to itself, activises cells of immune system (the active compound is ECHO group enterovirus, non-pathogen to humans and not causing immunesuppression, as influenza virus, e.g.).
The direct antitumoral effect of Rigvir is associated with oncotropism and oncolysis.
The cytolytic effect is selective – affects only malignant cells completely „ignoring” normal tissue cells. Very important is a fact that on the surface of non-lysated malignant cells Rigvir induce expression of tumor-associated differentiation antigens and subdues the expression of MAGE group antigens which are associated with progressive growth of melanoma. The altered surface structures of malignant cells makes them the target structures of cytotoxic mechanisms of the immune system.
The immunmodulating effect of Rigvir is associated with activation of lymphnodes, lymphoid tissue and immune cells. Inducing the immune response to itself, Rigvir stimulates normal primary and secondary immunogenesis and cancels tumour-caused block of local immunity. By activation of the immune response to the expressed tumor-associated antigens the apoptosis-like process of immune rejection of the tumour is realized. Repeated application of the preparation in the course of eficiently managed virotherapy with Rigvir allows to achieve gradual and complete regression of lymphnode micrometastases 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 increasement of cytotoxic CD8+ cells and helper – CD4+ cells. As well activation of the cells of nonspecific immunity: natural killers (NK) and macrophages is present. The function of lymphnode is activated and lymphocyte infiltration in tumour focus increases, which indicates to the activation of local immunity processes.
It had been convicingly proved that Rigvir do not multiply in other human organs, tissue and blood and is not excreted in the environment.
Virotherapy studies, either early – (before World War I and after World War II) or investigations in Latvia as well as conclusions of australian, german, japanese, US investigators in recent decades witnessed that oncotropism of viruses from different groups differs, and this phenomenon was called virus spectrum in regard to tumours and tumour spectrum in regard to viruses. The most sensitive to Rigvir are tumours of those organs and tissue which during the embryogenesis had originated fom endoplastum. We had determined that the tumours sensitive to Rigvir are:
- melanoma,
- gastric cancer,
- cancer of rectum and large intestine,
- cancer of pancreas,
- cancer of uterus,
- kidney tumours,
- cancer of bladder,
- different kinds of sarcoma:
- lymphosarcoma,
- angiosarcoma,
- rhabdomyosarcoma.
The sensitivity of melanoma to Rigvir was achieved by adaptation of ECHO-7 viruses in melanoma tissue.
Long term observations witnessed that cancer patients treated with Rigvir seldom are caught ill with viral diseases, including influenza.
Rigvir influence on the progress of melanoma
There are several goals of Rigvir systemic and local use before and after the surgery for the melanoma patients:
- To fullfil Rigvir potential oncotropic and oncolytic qualities against the tumour cells;
- To induce tumor cell tissue differentiation antigen genes, and reduction of tumor progression of gene expression, stimulate the immune rejection mechanism
- To delay and correct the immune deficit caused by surgery;
- For prevention of metastases process to activeate the regional lymph nodes after the primary focal surgery treatment to prevent the metastases process.
The results of Rigvir therapy
The assessment of therapeutic and immunomodulating effects of the usage of virotherapy treatment RIGVIR in the oncology clinic
The survival rate of skin melanoma patients who received RIGVIR after the primary resection of the focus
| Data of analyses (year), authors | Years of observation | Number of patients | Surgical treatment (ST) + Rigvir | Only surgical treatment (ST) |
| 1980-1982 (1983) Popena, MD | 3 | 149 | 84,0 | 54.5 |
| 1984-1986 (1987) Rudzitis, MD and Garklava, MD | 3 | 156 | 78,3 | 56.2 |
| 1987-1990 (1991) Rudzitis, Garklava, Popena, MD | 5 | 252 | 78,0 | 56.2 |
| 1993-1995 (1996) Probaka, MD. | >3 | 142 | 77,7 | 56.0 |
| 2004 – LOC О.Heisele, ChemD, L.Engele, MD etc. | 5 | 103 | 70 | 27 (as well as chemical therapy, radiation therapy etc.) |
Comparative results of the RIGVIR therapy for the melanoma patients or other immunomodulators depending on stage of the disease
| Stage | 5 years surveillance (%) | |
| RIGVIR + | Were not treated by RIGVIR | |
| II A | 92,6 (25/27) | 66,7 (2/3) |
| II B | 88,9 (8/9) | 28,6 (2/7) |
| II C / III | 76,5 13/17) | 14,3 (1/7) |
| IV | 60,0 (21/35) | 9,5 (2/21) |
The RIGVIR raised up survival rate in average of 40%.
The survival rate data of 85 patients, who received RIGVIR after the removal of the metastatic lymph nodes (in comparison with the immunomodulators С.Parvum, Decaris, Splenin).
In the analysis of 1991 detected that data of survival rate of patients with the melanoma of lower extremities were raised to 83%.
| 3-years survival rate (%) of the skin melanoma patients depending on localisation of the primary focus and the injection site of RIGVIR. | ||
| Localisation | RIGVIR injection in the area of м.gluteus | RIGVIR – regionally (in relation to the primary focus) |
| Head and neck1 | 68,0 | 87,5* |
| Arms2 | 72,1 | 100,0* |
| Legs2 | 83,0 | 94,0* |
Authors of the data analysis:
Prof. I. Chema, R.Bruvere, MD, O.Heisele , BiolD.
These data showed that it is very important to inject RIGVIR regionally in relation to the localisation of primary focus in the first months after the removal of it for the activation of sentinel lymph nodes.
Subsequently (after 2-3 years) it is necessary to activate also distant peripheral lymph nodes.
| 5-years survival rate of the colon tumour patients after RIGVIR therapy Onco-out-patient Department Hospital of Latvia – surgery (1979) | 41,0% |
| Surgery + RIGVIR (1979) | 71,2% |
Survival rate (%) of the eye melanoma patients after the enocculation and RIGVIR therapy
| Observations (years) | Number of patients Alive | (Number of patients) | Survival rate (%) |
| 1 | 74 | 74 | 100 |
| 2 | 51 | 49 | 96 |
| 3 | 40 | 36 | 90 |
| 4 | 28 | 23 | 82 |
| 5 | 19 | 14 | 71 |
The last analysis of the effect of treatment has been performed in 2004, analyzing a survival rate of 146 melanoma patients (after the removal of the primary focus starting from January 1990 to December 1992). The authors of data analysis: R.Bruvere, scientific MD, O.Heisele Scientific BiolD.
The Immunemodulating effect
RIGVIR activates phylogenetic caused activation of the immune system with the formation of specific antibodies. In sensitive tumours onkotropny RIGVIR virus inhibits the growth of cancer cell-specific antigens and induces a progressive expression of differentiation of tumor-associated antigēns (O.Heisele, BiolD).
| The expression of antigens MAGE on the surface of melanoma cells and their changes after the influence of RIGVIR | |||
| Group | Amount of studies | Expression of MAGE antigen | |
| Stimulation with RIGVIR before the surgery | 12 | 1/12 | 14,2 % |
| Placebo | 10 | 6/10 | 60,0% |
The history of investigation of Rigvir
In 1960 the scientists detected that the human intestinal viruses, obtained from young children, can destroy the human tumors which are engrafted to hamsters (Human heterograft of angiosarcoma in the cheek pouches of Syrian hamsters).
In 1965 laboratory of cancer virotherapy was established in Latvian Microbiology Institute to investigate this phenomenon. Under the guidance of Professor Aina Muceniece 60 different types of the enteroviruses were estimated.
In 1968 Ministry of Health of Latvian Republic accepted the first stage of clinical trial of 5 viruses with the the highest anti-tumour ability. EHCO-7 group virus with the highest anti-tumour activity, which was also proven as non-pathogen and epidemiologically safe, not able to replicate in healthy tissues, was named – Rigvir (Riga virus). RIGVIR was also successfully adopted in the skin melanoma tissues to test is against the most aggressive tumour, not sensitive to radiation and chemical therapy.
In 1985 the positive conclusion from the Scientific Council of Soviet Cancer Centre (Moscow) was received for the extensive clinical trials of using RIGVIR in the treatment of melanoma patients.
Since 1987, under permission of the Pharmacology Committee of Soviet Union, third stage of clinical trials were carried out in the Soviet Oncology Centre in Moscow and Saratov Oncology Hospital, where effectiveness and safety of RIGVIR was proven.
In April 29, 2004 the Rigvir preparation was registered in the State Agency of Medicines of Republic of Latvia.
Since 2008 Rigvir (as prescription drug) is available in pharmacy stores in Latvia.
The Therapy Process
The virotherapy treatment usually passes ambulatory. The individual course of therapy and injections for each patient is prescribed. The dose of one Rigvir injection is 2 ml (one vial). During the course of treatment, which usually lasts up to 3 years, patient receives approximately 22 -24 doses. Starting the treatment, the exact duration of treatment and number of doses will be determined individually, depending on the stage of disease and patient's immune system status, according to the guidelines, developed by scientists, who developed Rigvir, and available at the Latvian Virotherapy Center.
During the treatment patient's immune status and effect of the treatment shall be regularly monitored by means of different blood tests. After initial consultations at the Virotherapy Center and/or tumour excision, treatment could be continued under supervision of patient's local doctor, regularly contacting Virotherapy Center and oncologist / immunologist, who prescribed the treatment.
The best therapeutic effect is achieved if administering Rigvir regionally, this is why it is very important to follow recommendations of frequency, duration of injections and the site of the injections.
Consultative Office of the Latvian Virotherapy Center
The basic functions of Consultative Office:
- Consultations for the health care specialists – the practical use of virotherapy, assessment of the immune status
- Consultations for the melanoma patients before and after the surgery
- Consultation for the patient with disorders of the immune system
- Assessment of immune status by using of diagnostic method of the immune protection and progression of symptoms
- The registration of melanoma patients, actualization and regular monitoring of the immune status
Consultative office specialists, immunologists and oncologists, are trained and experienced in patient's treatment using Rigvir, the virus preparation with the immunomodulating and anti-tumor activity.
The Consultative Office is located in the Latvian Virotherapy Center:
Tirgonu Street 11, Old Riga, LV-1050, Latvia
Information and registration for the consultation (Registration in advance)
Phone +371 67229599
Mob.phone +371 27022303
Fax +371 67229555
e-mail: virotherapycenter@virotherapycenter.com
Contacts
Latvian Virotherapy Center
Tirgonu Street 11, Old Riga, LV-1050, Latvia
Phone +371 67229599; mob.phone +371 27022303, fax +371 67229555
e-mail: virotherapycenter@virotherapycenter.com; www.virotherapycenter.com
State Medical licence: code 010000929
VAT: LV40103195778
Bank details
State JSC "Mortgage and Land bank of Latvia"
Doma Square 4, Riga, LV-1977, LATVIA
Swift code: LHZBLV22
For partners
IBAN: LV16LHZB2100159447002
For patients
IBAN: LV16LHZB2100159447004
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