Comparison of the oncolytic activity of recombinant vaccinia virus strains LIVP-RFP and MVA-RFP against solid tumors

About authors

1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

2 Moscow Institute of Physics and Technology, Dolgoprudny, Russia

3 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

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

About paper

Funding: the development of oncolytic viruses and in vitro experiments were supported by the Russian Science Foundation (Russian Science Foundation grant № 20-75-10157); in vivo experiments were also supported by the Russian Science Foundation (Russian Science Foundation grant № 22-64-00057).

Author contribution: Ya Shakiba — literature analysis, pre-analytical work, in vitro and in vivo experiments, analysis and interpretation of data, preparation of figures and graphs; ER Naberezhnaya — in vitro experiments, data analysis and interpretation; D. V. Kochetkov — animal care, data interpretation; GM Yusubaleva — data visualization, manuscript editing; PO Vorobyev — production of preparative quantities of the virus for in vivo studies; VP Baklaushev — study planning, preanalytical stage of work, data analysis; AV Lipatova — research management, design development of recombinant strains, data interpretation, editing the manuscript.

Compliance with ethical standards: the study was approved by the ethics committee of the EIMB RAS (protocol № 3 dated October 27, 2022). Experiments carried out in accordance with Directive 2010/63/EU of the European Parliament and of the Council of Europe on the protection of animals used for research.

Received: 2023-02-20 Accepted: 2023-04-02 Published online: 2023-04-28

Among oncolytic viruses, modified vaccinia virus Ankara (MVA), a highly attenuated vaccinia virus (VV) is a well-studied variant with promising results in preclinical and clinical trials. The Lister VV strain from the Moscow Institute of Viral Preparations (LIVP) has been studied to a lesser extent than MVA and has a different oncolytic property from MVA. The aim of this work was to compare the oncolytic efficacy of LIVP and MVA strains against solid tumors. We developed recombinant variants LIVP-RFP and MVA-RFP; to enhance onco-selectivity thymidine kinase (TK) gene was inactivated by insertion of red fluorescent protein (RFP) gene to the TK locus. The replication kinetics and oncolytic activity of the obtained recombinant strains were evaluated in vitro and in vivo on tumor cell lines and mouse syngeneic tumor models of metastatic mouse 4T1 mammary adenocarcinoma, CT26 colon adenocarcinoma, and B16 melanoma. Both MVA-RFP and LIVP-RFP showed high replication efficiency in tumor cells and pronounced oncolytic activity against B16 melanoma and 4T1 breast adenocarcinoma allografts. In relation to 4T1, which is a model of triple negative human breast cancer, LIVP-RFP showed more than 50% increased cytotoxicity in in vitro tests compared to MVA-RFP, as well as a significant slowdown in the progression of 4T1 allografts and an increase in animal survival in experiments in vivo. Thus, the LIVP strain may be more promising than MVA as a platform for the development of recombinant oncolytic viruses for the breast cancer treatment.

Keywords: breast cancer, vaccinia virus, LIVP, MVA, viral oncolytic therapy, colon carcinoma, melanoma