Development of a recombinant oncolytic poliovirus type 3 strain with altered cell tropism

Hamad A1,2,3, Soboleva AV1, Vorobyev PO1, Mahmoud M1,2, Vasilenko KV4, Chumakov PM1, Lipatova AV1
About authors

1 Engelhardt Institute of Molecular Biology, Moscow, Russia

2 Moscow Institute of Physics and Technology (MIPT), Moscow, Russia

3 Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Moscow, Russia

4 Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Anastasia V. Lipatova
Vavilova, 32/1, Moscow, 119991, Russia; moc.liamg@vnaavotapil

About paper

Funding: the project was supported by the Russian Science Foundation (agreement number 20-75-10157 of 14 August 2020 “Research on the possibilities of obtaining recombinant strains of oncolytic viruses with tumor-specific replication and immunomodulatory protein expression”).

Author contribution: Chumakov PM, Lipatova AV — study concept and planning, data analysis; Hamad A, Vorobyev PO, Soboleva AV, Mahmoud M, Vasilenko KV, and Lipatova AV — laboratory experimental work; Hamad A, Soboleva AV, and Lipatova AV — preparation of figures and data interpretation.

Compliance with ethical standards: the study was conducted per the requirements of the World Medical Association Declaration of Helsinki 2000 and its subsequent revisions; in compliance with the principles of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes.

Received: 2022-04-18 Accepted: 2022-04-28 Published online: 2022-04-30

Diffuse gliomas are incurable, prevalent, and aggressive central nervous system tumors. Therefore, the development of selective oncolytic viral strains for malignant neoplasms is highly relevant. This study aimed to create an oncolytic virus based on a vaccine strain of poliovirus type 3 with natural antitumor activity. To achieve this goal, we replaced the internal ribosome entry site (IRES) of poliovirus with the corresponding fragment of human rhinovirus 30. The resulting recombinant oncolytic strain RVP3 retained the serotype of poliovirus type 3, as confirmed by virus neutralization micro-test with specific antiserum. In addition, the oncolytic efficacy of RVP3 was assessed in vitro on a broad panel of cell cultures. According to the results, RVP3 has changed its tropism, losing the ability to replicate in conditionally normal cell lines of embryonic astrocytes and embryonic fibroblasts while retaining the ability to replicate in tumor cells.

Keywords: oncolytic viral therapy, glioma, vaccine strain of poliovirus