With the ever-emerging concerns of patient safety during medical care, the search for treatments as safe as possible is a priority, especially when focusing on cancer treatment of which therapies often go hand in hand with severe side effects. Oncolytic virotherapy is an emerging treatment for cancer that is promising in both safety and efficacy. Many currently ongoing clinical trials demonstrate the growing interest in this field. To conduct clinical trials, preclinical studies are mandatory; however, there are not many reviews of toxicology studies on oncolytic virus therapies. This article summarizes the preclinical toxicology studies of the most well studied oncolytic viruses, including Oncorine, Talimogene laherparepvec, Cavatak, ONYX-015, teserpaturev and Rigvir, a non-pathogenic ECHO-7 virus. It is concluded that oncolytic viruses have been shown to have low toxicity and high tolerability in preclinical toxicology studies.Read More
Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and medical communities; therefore, the authors believe it is relevant to share their observations.Full Article
Alberts, P., Tilgase, A., Rasa, A., Bandere, K., Venskus, D.
Oncolytic viruses are a fast-developing cancer treatment field. Numerous viruses have been tested in clinical trials and three are approved. The first, Rigvir, is an immunomodulator with anti-tumor effect for treatment of cutaneous melanoma, local treatment of skin and subcutaneous metastases of melanoma, for prevention of relapse and metastasis after radical surgery registered in Latvia, Georgia, Armenia and Uzbekistan. The aim of the present review is to summarize the development of Rigvir…Full Article
Sorokins V., Tilgase A., Olmane E., Isajevs S., Zablocka T., Olmane E., Rasa A., Alberts P.
Melanoma is an aggressive skin cancer form with a grave prognosis. Current results suggest that oncolytic virus treatment of melanoma has a high therapeutic potential. ECHO-7 (Rigvir) is the first oncolytic virus registered in Latvia. A female patient was diagnosed with stage IIIB melanoma in December 2012, over 9.4 years ago. After the first excision and re-excision, the patient had several recurrences and disease progressions. After the patient had received surgical treatment in 2014, ECHO-7 virus oncolytic virotherapy was started. Since then, the patient has experienced only one more disease progression episode in May 2015 and has been stable for over 60 months. The patient has not received any other treatment than surgery and oncolytic virotherapy. No severe adverse events have been reported during virotherapy. The present case suggests that ECHO-7 virotherapy is an effective treatment of skin melanoma.Full Article
Elizabete Pumpure, Eva Dručka, Dana Kigitoviča, Raimundas Meškauskas, Sergejs Isajevs, Ineta Nemiro, Agnija Rasa, Evija Olmane, Tatjana Zablocka, Pēteris Alberts, Simona Doniņa
Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression‐free survival are good.Full Article
Proboka G., Tilgase A., Isajevs S., Zablocka T., Olmane E., Rasa A., Alberts P.
Adrenal gland melanoma is an extremely rare diagnosis with less than 20 cases reported. The criteria for diagnosing adrenal gland melanoma include involvement of only one adrenal gland, presence of melanin pigment in the histological examination of the tumor tissue, no primary melanoma tumor in any other organ, and no history of resection of pigmented lesions. However, it is complicated to rule out melanoma of unknown primary origin. Here we report a female patient who at the age of 75 years was admitted to hospital due to suspicion of adrenal and gastric tumor. The largest tumor was found in the adrenal gland, thus leading to the diagnosis of primary adrenal gland melanoma presenting metastases in the stomach. The melanoma was BRAF wild type. Due to the rarity of this disease, there is no standard treatment. After two subsequent surgeries, treatment with the ECHO-7 oncolytic virus Rigvir was started. The patient has received oncolytic virotherapy for 5 years and 1 month and has been stable since then with good tolerability. The therapy is still ongoing. Adrenal gland melanoma is an extremely rare diagnosis and therefore it is important to discuss the diagnostic criteria and possible treatments.Full Article
Andra Tilgase, Lita Grīne, Ilze Blāķe, Mārtiņs Borodušķis, Agnija Rasa & Pēteris Alberts
Uveal melanoma is a rare intraocular malignancy. Half of the patients diagnosed will develop metastases within 10 to 30 years, most commonly in the liver. Although there has been a significant development in the treatment of melanoma, no effective treatment to prevent or treat metastases of uveal melanoma is available. Oncolytic viruses are now being studied for various types of cancers and show promising results. Preclinical results show cytolytic activity of enteric cytopathic human orphan virus type 7 (ECHO-7) strain Rigvir in human melanoma, rhabdomyosarcoma, gastric adenocarcinoma, lung carcinoma and pancreas adenocarcinoma cell lines. The aim of this study was to test the possible cytolytic activity in human uveal melanoma cell lines.Full Article
Jaunalksne I., Brokāne L., Petroška D., Rasa A., Alberts P.
This report describes a stage I uveal melanoma patient treated with oncolytic virus Rigvir as an adjuvant therapy.Full Article
Proboka G., Rasa A., Olmane E., Isajevs S., Tilgase A. Alberts P.
Laryngeal cancer can cause irreversible damage to the vocal cords, resulting in loss of voice. This report describes a stage III glottic cancer patient treated with Rigvir therapy, showing good response to treatment and with laryngeal functions still preserved.Full Article
Brokāne L., Jaunalksne I., Tilgase A., Olmane E., Petroška D., Rasa A., Alberts P.
Advances in the understanding of cancer immunotherapy and the development of multiple checkpoint inhibitors have dramatically changed the current landscape of cancer treatment. However, checkpoint inhibitors actually help only the minority of patients. Combining checkpoint inhibitors with oncolytic virotherapy can be a gamechanger. Multiple viruses are currently being tested in clinical trials in combination with anti-PD-1 or antiCTLA-4 antibodies, and thus far the results have been encouraging, particularly, response rate of combined therapy with checkpoint inhibitors (PD1) may exceed 60%. While the first finalized registration studies combining virus and Checkpoint inhibitors should be expected not faster than in 2022, RIGVIR is already successfully used by doctors, thus improving the efficacy of Checkpoint inhibitors not causing additional side effects. Please, be familiar with recent publication – case report about a 35‐year‐old male patient who was diagnosed with stage IIC skin melanoma that rapidly progressed after surgery. Treatment was continued with radiotherapy, which did not stop further spread of disease and the patient was put on a combination of nivolumab and Rigvir. Subsequently, the progression has slowed.Full Article
Ismailov Z., Rasa A., Bandere K., Brokāne L., Tilgase A., Olmane E., Nazarovs J., Alberts P.
Renal cell carcinoma is the most commonly diagnosed primary malignant tumor of the kidney in adults, and includes the variant of chromophobe renal cell carcinoma. Despite new targeted therapies that improve progression-free survival (PFS) and overall survival (OS) for early-stage renal cell carcinoma, the 5-year survival for patients with stage IV renal cell carcinoma remains below 10%, and the 50% OS is less than one year. Metastatic renal cell carcinoma can be resistant to cytotoxic chemotherapy. This report is of a case of stage IV chromophobe renal cell carcinoma that responded well to treatment with the oncolytic ECHO-7 virus, Rigvir®.Full Article
Tilgase, A., Olmane, E., Nazarovs, J., Brokāne, L., Erdmanis, R., Rasa, A., Alberts, P.
Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The treatment consists of surgical resection, systemic chemotherapy, and new biological agents. One more recently emerging treatment option is oncolytic virotherapy. Although the use of the new treatment methods shows improved overall and progression-free survival, in general, even with the new treatments, mortality remains high and combinations of treatments should be sought to treat patients with colorectal cancer…Full Article
Proboka, G., Tilgase, A., Isajevs, S., Rasa, A., Alberts, P.
Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease…Full Article
Alberts, P., Olmane, E., Brokāne L., Krastiņa, Z., Romanovska, M., Kupčs, K., Isajevs, S., Proboka, G., Erdmanis, R., Nazarovs, J., Venskus, D.
Oncolytic virotherapy is a recent addition to cancer treatment. Here, we describe positive treatment outcomes in three patients using RIGVIR® virotherapy…Full Article
Tilgase, A., Patetko, L., Blāķe, L., Ramata-Stunda, A., Borodušķis, M., and Alberts, P.
The role of oncolytic viruses in cancer treatment is increasingly studied. The first oncolytic virus (RIGVIR®, ECHO-7) was registered in Latvia over a decade ago. In a recent retrospective study RIGVIR® decreased mortality 4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study are to test the effect of RIGVIR® on cell line viability in vitro and to visualize the cellular presence of RIGVIR® by immunocytochemistry…Full Article
Doniņa, S., Strēle, I., Proboka, G., Auziņš, J., Alberts, P., Jonsson, B., Venskus, D., Muceniece, A.
An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (RIGVIR®) is approved and registered for virotherapy, an active and specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of RIGVIR® in substage IB, IIA, IIB and IIC melanoma patients on time to progression and overall survival…Full Article
Clinical studies of RIGVIR® began in 1968 in Riga, LatviaRead More