RIGVIR

RIGVIR is a virotherapy medication approved by the State Agency of Medicines of the Republic of Latvia.^[1] It was developed in the 1960s and 1970s by the team of Aina Muceniece (1924–2010) and patented in 2002.^[2]

Virions of enteroviruses in Rigvir

Rigvir is a drug that contains live, natural virus, which has cytolytic and immunomodulating effects. Cytolytic action – finding and destroying malignant cells, applies only to the cancer cells without affecting the normal tissue cells. Regarding immunomodulation, because of its structure Rigvir selectively affects cells in sensitive tumors. Rigvir activates cells of the immune system due to what causes specific immune response against itself. It is not genetically modified and not pathogenic virus, it is not able to replicate in human body. It is issued in oncology for the prevention of secondary immunodeficiency. In 2015 RIGVIR was registered in Georgia^[3] and included in the Latvian national guidelines for skin cancer and melanoma treatment.

Recent retrospective study published in Melanoma Research showed that IB-IIC melanoma patients treated with oncolytic virus Rigvir were 4.39–6.57-fold lower mortality than those, who according to melanoma treatment guidelines did not receive virotherapy and were only observed.^[4]

Passed all phases of clinical trials and registered in Latvia (Reg. No.: 04-0229) and is used as a prescription drug for the treatment of cancer. Rigvir – 7 strain ECHO-virus, a solution for intramuscular injection. Code: ATX: L03AX. Must be stored and transported at a temperature of -20 °C ± 2 °C.

History

Rigvir antigen in tumor cells

• In 1960 unknown phenomenon was discovered: when human enteric viruses (enteroviruses of group ECHO), which were isolated from the gastrointestinal tract of young children and grafted into hamster buccal bags showed oncotropic and oncolytic properties^[5]
• In 1965, cancer virotherapy laboratory was founded in the Institute of Microbiology (Latvian Academy of Sciences) to explore this phenomenon. 60 different types of enteric viruses were tested, 5 of them were identified as the most effective viruses capable of destroying cancer cells. One of them was named Rigvir (Riga virus). It was found that Rigvir is safe for adults and not able to replicate in the human body.^[6]
• In 1968 scientists received permission from the Ministry of Health of the Latvian SSR to study and use Rigvir on patients, with the participation of 415 patients. It has been proven that Rigvir was safe for cancer patients and can not cause epidemics. Successful adaptation of the virus in the tissues of cutaneous melanoma (not sensitive to chemotherapy and radiotherapy) was produced, and the therapeutic effect was ascertained.^[7]
• In 1985, received approval from the All-Union Cancer Center in Moscow to begin an extensive clinical research of Rigvir treatment on melanoma patients (study involved 1063 patients).
• In 1987 clinical studies also took place in the All-Union Cancer Center in Moscow and Saratov oncology clinic. It was acknowledged that Rigvir is not dangerous even for very severe and incurable patients.
• In 1990–1995, Rigvir used to treat patients with various kinds of cancer in the P. Stradina clinic and Latvian Oncology Center.
• On October 20, 2002 granted a patent for Rigvir.
• On April 29, 2004 Rigvir was approved by the State Agency of Medicines of the Republic of Latvia.
• On August 22, 2005 Rigvir became available for residents of Latvia.
• Since 2011 Rigvir is included in the list of state compensated drugs to the diagnosis of malignant melanoma of the skin (the exception – ocular melanoma) for residents of Latvia.
• In February 2015 registered in Georgia.^[3]
• Since 2015 Rigvir is included in the Latvian National guidelines for treatment of skin cancer and melanoma.

Side effects

Like other medicines, Rigvir may cause side effects. The side effects are short-term and do not require special therapy, the most common side effects are subfebrile temperature, pain in the tumor, fatigue, drowsiness, dyspepsia (diarrhea).^[8]

See also

• Oncolytic virus

References

1. For an freely accessible English version see page 642 of Chumakov PM, Morozova VV, Babkin IV, Baikov IK, Netesov SV, Tikunova NV (2012). "Oncolytic enteroviruses" (PDF). Molecular Biology 46 (5): 639–50. doi:10.1134/S0026893312050032.
   For the original version in Russian see Chumakov PM, Morozova VV, Babkin IV, Baĭkov IK, Netesov SV, Tikunova NV (2012). "[Oncolytic enteroviruses] (Russian).". Molekulyarnaya Biologiya 46 (5): 712–25. PMID 23156670.
2. "Inventions and Inventors of Latvia". Retrieved 8 April 2013.
3. "Georgia Today".
4. Doniņa, Simona; Strēle, Ieva; Proboka, Guna; Auziņš, Jurģis; Alberts, Pēteris; Jonsson, Björn; Venskus, Dite; Muceniece, Aina (2015). "Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in melanoma patients after surgical excision of the tumour in a retrospective study". Melanoma Research 25 (5): 421–426. doi:10.1097/CMR.0000000000000180.
5. . Muceniece A.J. 1978. Analysis of sensitivity of human melanomas to enteroviruses adaptred to these tumors.In: Virusy v terapii opukholei (Viruses in Antitumor Therapy), Riga: Zinatne, pp. 175–189.
6. Muceniece A.J., Bumbieris J.V. 1982. Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya geterogenizatsiya opukholei (Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217–234.
7. Muceniece A.J., Bumbieris J.V. 1982. Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya geterogenizatsiya opukholei (Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217–234
8. "RIGVIR side effects".

External links

• Latvian Virotherapy Center