Oncolitical viruses in the therapy of malignant neoplastic diseases

Клаан, Н. К.; Akin'shina, L. P.; Pronina, T. A.

doi:10.17650/1726-9784-2018-17-4-6-19

Rossijskij bioterapevtičeskij žurnal

2019

DOI: 10.17650/1726-9784-2018-17-4-6-19

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Oncolitical viruses in the therapy of malignant neoplastic diseases

Н. К. Клаан

L. P. Akin'shina

T. A. Pronina

Abstract: The main types of oncolytic viruses and the mechanisms of their action on the tumor cells are described in this review. Examples of optimization of the viral genome are given with a view to enhancing the oncolytic properties of the virus. The achievements in the field of development of antitumour agents based on oncolytic viruses and methods of their application in oncology are described.

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Cited by 2 publications

References 101 publications

(129 reference statements)

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Preclinical Safety Assessment of Antineoplastic Agents Based on Live Non-Pathogenic Enteroviruses

Sivak,

Stosman,

Kalinina

et al. 2024

Bezopasnost' i risk farmakoterapii

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INTRODUCTION. Developing novel medicines based on non-pathogenic enterovirus strains exhibiting oncotropic and oncolytic properties represents an up-to-date and safe approach to complex cancer treatment and postoperative metastasis prevention. Safety pharmacology studies are a necessary step in the preclinical development of medicinal products.AIM. The study aimed to investigate the single and repeated-dose general toxicity, local tolerance, safety pharmacology, and pyrogenicity of medicinal products based on non-pathogenic LEV4, LEV7, LEV8, LEV14, and Russo enterovirus strains as part of preclinical safety studies.MATERIALS AND METHODS. The study used medicinal products of highly purified group A, B, and C enteroviruses at a titre of 2×107–5×108 CPD50/mL (CPD50 is a cytopathogenic dose of the virus causing 50% cell lysis) and normal saline as a diluent. The viruses were propagated in Vero cells. The safety study used 220 male and female BALB/c mice, 440 male and female Wistar rats, and 18 male Soviet chinchilla rabbits. The study animals received an intravenous dose of 1×105 or 1×106 CPD50/animal once (single-dose toxicity) or weekly for 90 days (repeated-dose toxicity). Clinical examination, laboratory testing, and necropsy were performed on days 45 and 91 of the experiment. Statistical data processing was performed using Prism 8.0 software (GraphPad Software, Inc., USA).RESULTS. Upon single administration of each of the five enterovirus medicinal products to mice and rats, the authors observed complete survival, upward trends in body weight gain, and no gross or histopathological changes in the brain, spleen, liver, kidneys, lungs, or at the injection site. Upon repeated administration at the study doses, the medicinal products caused no functional changes in the organs and systems. All the studied parameters were within the normal physiological ranges for male and female rats. Histopathological examination revealed no pathological changes or specific cytolytic and/or cytopathic effects. No local irritation was observed. None of the investigational medicinal products showed pyrogenicity.CONCLUSIONS. The obtained preclinical results demonstrate the safety of antineoplastic agents based on live non-pathogenic LEV4, LEV7, LEV8, LEV14, and Russo enteroviruses.

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Preclinical Safety Assessment of Antineoplastic Agents Based on Live Non-Pathogenic Enteroviruses

Sivak,

Stosman,

Kalinina

et al. 2024

Bezopasnost' i risk farmakoterapii

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Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines

Nazarenko,

Biryukova,

Orlova

et al. 2023

Problems of Virology

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Introduction. Flaviviruses, possessing natural neurotropicity could be used in glioblastoma therapy using attenuated strains or as a delivery system for antitumor agents in an inactivated form. Objective. To investigate the sensitivity of glioblastoma and pancreatic carcinoma cell lines to vaccine strains of yellow fever and tick-borne encephalitis viruses. Materials and methods. Cell lines: glioblastoma GL-6, T98G, LN-229, pancreatic carcinoma MIA RaCa-2 and human pancreatic ductal carcinoma PANC-1. Viral strains: 17D yellow fever virus (YF), Sofjin tick-borne encephalitis virus (TBEV). Virus concentration were determined by plaque assay and quantitative PCR. Determination of cell sensitivity to viruses by MTT assay. Results. 17D YF was effective only against pancreatic carcinoma tumor cells MIA Paca-2 and had a limited effect against PANC-1. In glioblastoma cell lines (LN229, GL6, T98G), virus had no oncolytic effect and the viral RNA concentration fell in the culture medium. Sofjin TBEV showed CPE50 against MIA Paca-2 and a very limited cytotoxic effect against PANC-1. However, it had no oncolytic effect against glioblastoma cell lines (LN229, T98G and GL6), although virus reproduction continued in these cultures. For the GL6 glioblastoma cell line, the viral RNA concentration at the level with the infection dose was determined within 13 days, despite medium replacement, while in the case of the LN229 cell line, the virus concentration increased from 1 × 109 to 1 × 1010 copies/ml. Conclusion. Tumor behavior in organism is more complex and is determined by different microenvironmental factors and immune status. In the future, it is advisable to continue studying the antitumor oncolytic and immunomodulatory effects of viral strains 17D YF and Sofjin TBEV using in vivo models.

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Oncolitical viruses in the therapy of malignant neoplastic diseases

Cited by 2 publications

References 101 publications

Preclinical Safety Assessment of Antineoplastic Agents Based on Live Non-Pathogenic Enteroviruses

Preclinical Safety Assessment of Antineoplastic Agents Based on Live Non-Pathogenic Enteroviruses

Investigation of oncolytic potential of vaccine strains of yellow fever and tick-borne encephalitis viruses against glioblastoma and pancreatic carcinoma cell lines

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