The world's first oncolytic virus was clinically approved in 2004 in Latvia. Clinical trials of this virus began in the 1960s under the supervision of Latvian scientist, Professor Aina Muceniece.
In 1965 the Cancer Virotherapy Laboratory was established within the A. Kirhensteins Institute to study various types of enteroviruses and to examine whether or not they are capable of destroying human cancers. 60 types of enteroviruses were examined and five of the most active cancer cell destroyers were discovered. One of them was named the Riga Virus. Studies have established the safety of the Riga Virus and its inability to multiply in the healthy cells of an adult body.
Clinical studies began in 1968 in Riga, Latvia. More than 700 patients who had been diagnosed with late stage melanoma, stomach and gastrointestinal tract cancer were involved in the pre-registration safety and efficacy studies [1-5].
Approximately 190 late stage melanoma, stomach and gastrointestinal tract cancer patients were involved in safety studies [6-9]. The most commonly observed side effects were sub-febrile temperatures, pain in the tumour area, fatigue, sleepiness and dyspepsia; all were reversible and only lasted for a couple of days. No intolerance or treatment related side effects were observed after the discontinuation of treatment.
More than 540 melanoma patients were involved in efficacy studies. These studies showed that overall survival was prolonged for patients who had been treated with the Riga Virus compared with those who had only been treated with surgery*. The main Riga Virus clinical studies showed increased 3-year survival in melanoma patients [1, 10-18]. The 3-year survival rate for patients who had been treated only with surgery was between 46-58%, while patients who had also been treated with the Riga Virus had a 3-year survival rate between 57-84% and a 5-year survival rate between 44-66%. The 3- and 5-year survival rates for eye melanoma patients were 90% and 70%, respectively.
The safety studies also yielded survival data in the approximately 160 stomach and gastrointestinal tract cancer patients who participated. Thus, for stage III stomach cancer patients the 5-year survival post-surgery rate was 24-33%, compared with 47-60% for those who had also been treated with the Riga Virus. Furthermore, for stage II-IV rectum cancer patients the 5-year post-surgery survival rate was 41-68%, compared with 71-78% for those who had also been treated with the Riga Virus [1, 5, 19, 20].
* Today 5-year survival rate data is required for registration, while most drugs registered at the turn of the 20th and 21st centuries (which are still widely used) didn’t require such data at the time of approval. Interestingly, the Rigvir® clinical studies conducted during the 1970s and 1980s recorded both 3- and 5-year survival rates.
1. Brūvere, R., O. Heisele, A. Ferdats, A. Rupais, and A. Muceniece, Echovirus-mediated biotherapy for malignant tumours: 40 years of investigation. Acta medica Lituanica, 2002. Suppl. 9: p. 97-100.
2. Doniņa, S., I. Strēle, G. Proboka, J. Auziņš, P. Alberts, B. Jonsson, D. Venskus, and A. Muceniece, 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, 2015. 25(5): p. 421-426.
3. Alberts, P., E. Olmane, L. Brokāne, Z. Krastiņa, M. Romanovska, K. Kupčs, S. Isajevs, G. Proboka, R. Erdmanis, J. Nazarovs, and D. Venskus, Long-term treatment with the oncolytic ECHO-7 virus Rigvir of a melanoma stage IV M1c patient, a small cell lung cancer stage IIIA patient, and a histiocytic sarcoma stage IV patient-three case reports. APMIS, 2016. 124(10): p. 896-904.
4. Alberts, P., L. Brokāne, G. Proboka, D. Venskus, I. Jaunalksne, D. Reihmane, A. Tilgase, V. Telle, L. Patetko, A. Ramata Stunda, and M. Borodušķis, Virotherapy as an independent therapy in oncology: The Latvian model. (In Latvian: Viroterapija kā patstāvīga terapija onkoloğijā: Latvijas modelis.). Latvijas Ārsts, 2016. 5: p. 60-63.
5. Brūvere, R., O. Heisele, A. Ferdats, A. Rupais, and A. Muceniece, Echovirus-mediated biotherapy for malignant tumours: 40 years of investigation. Third Baltic Congress of Oncology, 2-4 May, Vilnius, Lithuania, 2002(Abstract 216): p. 251.
6. Konopatskova, O.M., A.N. Tahtamish, and I.N. Pavlova, Results of the use of the immunomodulator Rigvir in skin melanoma patients (In Russian). National scientific conference on Cancer Biotherapy, Moscow, 18-20 June, 2002.
7. Priedīte, I., R. Garklava, R. Bruvere, L. Vitolina, and A. Muceniece, Results from treatment of rectal cancer (In Russian). III Conference of Estonian, Lithuanian and Latvian oncologists, Riga, 1971: p. 325.
8. Januskevics, V.J., B. Popena, and I. Priedite, Postoperative immunostimulation of patients with colorectal cancer., in Modulation of postoperative anti-tumor immunity (In Russian). 1988, Zinatne: Riga. p. 95-101.
9. Kunicina, T.A., J.J. Dmitrievs, and S.L. Tihova, Monitoring of the immunity of skin melanoma patients during the treatment with an enterovirus (In Russian). Symposium "The symptoms and treatment of skin melanomas." Saratov, 13-14 Sept., 1990.
10. Heisele, O., The effect of a viral immunomodulator on the immune reactivity of patients with skin malignant melanoma (In Russian) Thesis. 1987: p. 1-166.
11. Rudzītis, M., R. Garklāva, B. Popēna, and I. Desjatnikova, Increased five-year survival of skin melanoma patients undergoing surgical treatment followed by immunomodulator treatment (In Russian). All-Union Symposium "Current issues of immunotherapy of tumours", Jūrmala, Latvia 19-21 April, 1988. 2:pp. 19-20.
12. Grigalinovičs, H., M. Rudzītis, M. Skudra, B. Popēna, I. Desjatnikova, and R. Garklāva, Effect of a viral immunomodulator (Rigvir®) on the morphology and survival of cutaneous melanoma patients (In Russian). Proceedings of the Latvian Academy of Sciences, 1988. 497(12): p. 72-75.
13. Muceniece, A., M. Rudzītis, R. Brūvere, I. Desjatnikova, A. Ferdats, R. Garklāva, O. Heisele, B. Popēna, and A. Volrāte, A specially selected and adapted human enterovirus as a biological response modifier with antitumor activity in the treatment of human malignant skin melanoma. Second International Conference on Melanoma, Venice, Poster Sessions, 16-19 October., 1989: p. 316.
14. Ferdats, A., Viruses as immunomodulators of antitumour activity (In Russian). Thesis. 1989: p. 1-355.
15. Muceniece, A., Rigvir - development of a viral immunomodulator and cancer virotherapy clinical trials (In Latvian). The 4th Latvian Congress of Physicians, Riga, 2001: p. 126-127.
16. Čēma, I., G. Proboka, J. Tārs, A. Skağers, E. Kornevs, A. Muceniece, A. Bīgestāns, and G. Lauskis, Melanoma of the facial skin and oral mucosa (In Latvian). The 4th Latvian Congress of Physicians, 2001: p. 52.
17. Brūvere, R., G. Feldmane, A. Ferdats, O. Heisele, and A. Muceniece, Adjuvant immunotheraphy with virus-mediated biomodulators developed in Latvia: experimental and clinical data. Abstracts of the Perspectives in Melanoma X and The Third Annual International Melanoma Research Congress 14-16 September, Noordwijk, The Netherlands. Melanoma Research, 2006. 16(Suppl 1): p. S34-ABS-0058.
18. Muceniece, A. and D. Venskus, How to assess immunity - the melanoma model. (In Latvian: Kā vērtēt imunitāti - melanomas modelis). 2007.
19. Garklāva, R., I. Priedite, and A. Muceniece, Long-term results of surgical treatment of patients with gastric and rectal cancer after immunostimulation with a nonpathogenic enterovirus., in Immunocompetence and immunotherapy of cancer patients (In Russian). 1981: Kemerovo. p. 77-91.
20. Muceniece, A., Cancer virotherapy. 1. Retrospection and justification (In Latvian: Ļaundabīgo audzēju viroterapija. 1. daļa - retrospekcija un pamatojums). Doctus, 2005. Nov.: p. 40-44.
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