Pre-Clinical Research

We are constantly searching evidence for new indications of oncolytic virotherapy application and the pre-clinical data is promising.

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4-Week repeated dose rat GLP toxicity study of oncolytic ECHO-7 virus Rigvir administered intramuscularly with a 4-week recovery period

Published: Toxicology Reports. 19 January 2021

Authors: Katarzyna Piwonia, Gilta Jaeckela, Agnija Rasa, Pēteris Alberts.
Charles River Laboratories Edinburgh Ltd.

The objectives of this study were to determine the potential toxicity of Rigvir, an ECHO-7 oncolytic virus, when administered intramuscularly for 4 weeks to rats, with a 4-week recovery period, and to evaluate the reversibility of any potential findings. In addition, the biodistribution of Rigvir in selected tissues was determined.

There were no unscheduled deaths, adverse clinical signs, no changes in body weight, body weight gain, food intake, ophthalmoscopy, clinical pathology, urine volume or composition, or organ weights. Slightly higher numbers of eosinophils in Rigvir treated animals returned to normal after recovery. Rigvir biodistributed to the spleen. Low incidence of inflammatory cell infiltration at administration sites and increased lymphoid cellularity at the regional (inguinal and popliteal) lymph nodes were observed; after recovery, only those in popliteal lymph nodes remained. Therefore, 4-week Rigvir at 2×107 TCID50 administration was well tolerated in rats. The no-observed-adverse-effect level (NOAEL) was the highest dose tested, 2×107 TCID50.

Effect of the oncolytic ECHO-7 virus RIGVIR® on the viability of cell lines of human origin in vitro

Published: 2018. Journal of Cancer. 28 February 2018; 9(6): 1033-1049. doi: 10.7150/jca.23242.

Area: IVC, Riga, Latvia; Faculty of Biology, University of Latvia, Riga, Latvia.

Authors: Tilgase, A., Patetko, L., Blāķe, L., Ramata-Stunda, A., Borodušķis, M., and Alberts, P.

Graphical abstract:
Viability of cancer cells of human origin (gastric adenocarcinoma (AGS; CRL-1739), lung carcinoma (A549; CCL-185), Melanoma (FM-9)

Source: A.Tilgase et J.Cancer 2018 Feb ( And L. Patetko et al. (unpublished)

ECHO-7 Oncolytic Effect: Time and Dose Dependent (Control (●); with Echo-7 1% ();with ECHO-7 10%())

Source: A.Tilgase et J.Cancer 2018 Feb ( And L. Patetko et al. (unpublished)

Effect of oncolytic ECHO-7 virus strain Rigvir on uveal melanoma cell lines

Published: BMC Research Notes. 16 April 2020

Authors: Tilgase A., Grīne L., Blāķe I., Borodušķis M., Rasa A. and Alberts P.

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.

The results suggest cytolytic activity of oncolytic ECHO-7 virus strain Rigvir in MP41, 92-1 and Mel-202 cell lines.

Biomarker development

As a progressive biomanufacturer we are aware of the great genetic diversity of patients and every type of cancer, thus the use of personalized medicine and biomarkers is one of our main developmental objectives. Biomarkers allow a much faster assessment of the course of treatment and increase the effectiveness of treatment by applying medication, regardless of indication, primarily focusing on genetic features of tumor or patient.

With our significant amount of treatment experience, we are actively working on a line of biomarkers, that demonstrate compliance and efficiency with oncolytic virotherapy, including the cases of early-stage treatment.

ECHO-7 action in melanoma cells