Latvian Virotherapy center

The studies on usage of viruses in therapy of malignant tumours intensively are taking place all over the world. Already now it may be stated that the world’s scientists increasingly prefer the virotherapy as the alternative future therapy.
Due to the excellent achievement of the scientists – the only known virus called Rigvir with the immunoactivating and destructive properties of tumor cells which is developed and introduced into medical practice, Latvia has become the world’s leader in virotherapy field, and for the reason the development would not stop at the achieved level and Latvia would not lose it’s leader position the Virotherapy centre of Latvia was established in October, 2008 by Latvia’s scientists, immunologists and oncologists.

Virotherapy centre tasks and future goals:

• The promotion of the development of virotherapy as practical medicine and a promising and perspective science
• The organization of trainings in practice of virotherapy and assessment of immune status
• The implementation of medical consultations
• Support of scientific research, scientific publishing
• 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 defence against the tumour was not implemented not due to the lack of surface antigens in the tumour, but due to the fact that the tumour successfully avoids from the immune control and inhibits/blocks all the immune reactions targeted to the tumour. That’s why it is important in oncology to use the protective activities of the immune mechanisms, promotors of stabilization and preparations that change the surface structures of the tumour cell. Such properties possess 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.

* Apoptosis is a natural process of the liquidation of old, damaged and foreign cells.

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 radical operation for the prevention of metastases. You can not expect the effect of biotherapy in the late stages of cancer, and after all possible treatments have been exhausted.
The types (methods) of use of virotherapy are local and systemic. Virotherapy has to be combined with other methods used in oncology, such as operation, radiotherapy and chemotherapy, hormonal therapy. In such combinations the suppression of immunity (the effect of immunosuppression) is reduced due to the above methods of treatment effect. Virotherapy is very important in the treatment of 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. It is important to monitor the immune status and consult immunologist during the virotherapy.

For the practical use of virotherapy Latvian scientists and practicing immunologists under the guidance of Professor Aina Muceniece have worked out the guidelines which recommend the frequency and duration of virotherapy course, as well as the virus injection site for the higher therapeutic effect – according to the principle of regional administration.

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

Is a 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 enable 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,
• colorectal cancer,
• pancreatic cancer,
• kidney cancer,
• bladder cancer,
• prostate cancer,
• lung cancer,
• uterine cancer,
• various types of sarcoma:
  • lymphosarcoma,
  • angiosarcoma,
  • rhabdomyosarcoma,
  • reticulosarcoma.

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*

* p<0,05
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 the laboratory of cancer virotherapy was organised to investigate this phenomenon. Under the guidance of Professor Aina Muceniece 60 different types of the intestinal viruses were estimated and 5 the most active destroyers of the tumour cells were obtained. One of them was named – Rigvir (Riga virus).
The safety and non-ability of Rigvir to multiple in the healthy tissue is established.
The safety for the patients and epidemiological safety of RIGVIR was proven.
The adaptation of RIGVIR in the skin melanoma tissues was started because this tumor is not sensitive to radiation and chemical therapy. The adaptation of RIGVIR in the melanoma is successful and the therapeutic effect of RIGVIR adapted in melanoma was detected.


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.

In 1987 the clinical trials were also done in the Soviet Oncology Centre in Moscow and Onco-Outpatient Department Hospital of Saratov with the permission of the Pharmacology Committee of Soviet Union where the safety of RIGVIR for even very difficult, untreatable patients was approved.

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 or injections for every patient is prescribed. The dose of rigvir is 2 ml (one vial). During the course of treatment which should be long-lasting - up to 3 years- the patient receives approximately 22 -24 doses. The exact duration of treatment and number of doses must be determined individually depending on the stage of disease, the immune status of patient when starting the treatment and according to developed guidelines which are available in the Virotherapy Centre of Latvia.
Between the courses the immune status of patients and effect of the drug is monitored regularly using different blood tests. It is possible to continue the treatment under the supervision of your doctor after initial consultations and/or tumour excision, but the patient should regularly get in contact with oncologist/immunologist, who prescribed the treatment.
During the treatment it is important to prescribe the right frequency and duration of injections course for the better therapeutic effect as well as the injection site of virus - according to the principle of regional administration.

Consultative Office of Virotherapy Centre of Latvia

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

Specialists of the Consultative Office – immunologists and oncologists are experienced to use the only virus treatment with the anti-tumor activity – Rigvir

The Consultative Office is located in Virotherapy Centre of Latvia:

Teatra Street 9, Old Riga, LV-1050, Latvia

Information and registration for the consultation (Registration in advance)

Telephone number: +371 67229599
Mobile phone number: + 371 27022303