Perspectives for applying Alphaviruses in antitumor therapy

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Abstract

Oncolytic viral therapy is a promising approach for treating tumors. Oncolytic viruses can directly lyse tumor cells and indirectly activate antitumor immunity. Alphaviruses, as oncolytic viruses, are particularly promising agents because they can selectively infect and lyse tumor cells, modulate microtumor environment, elicit immune-mediated lysis of tumor cells, and serve as a platform for transgene delivery. To ensure safety, attenuated strains of Alphaviruses are typically used for genetic engineering, and immunogenic tumor-associated antigens or cytokines are commonly chosen as transgenes. Studies evaluating both in vitro and in vivo oncolytic and immunomodulatory effects of Alphaviruses and vectors based on them have been growing exponentially. Animal models of various tumor types were used to examine the effectiveness of Alphaviruses, including Sindbis, Semliki Forest virus, Geta (strain M1), Venezuelan equine encephalitis virus, and vectors based on them. Additionally, Alphaviruses revealed enhanced antitumor activity while used in combination therapies with other oncolytic viruses. Alphavirus-like replicon particles based on attenuated Venezuelan equine encephalitis virus may serve for transgene delivery to express heterologous proteins at high levels, and induce both humoral and cellular immune responses. An alphaviral vector-based vaccine, encoding the HER2 extracellular and transmembrane domains, has demonstrated safety and efficacy in preclinical mouse models, as well as in phase I clinical trials for advanced breast cancer patients with HER2 overexpression. This vaccine is known to be safe, effective, and capable of inducing T-cell immunity. In this review, we discuss the current progress in preclinical and clinical investigations, as well as the future potential of Alphaviruses for oncolytic virotherapy.

About the authors

Alina S. Nazarenko

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Author for correspondence.
Email: nazarenko_as@chumakovs.su
SPIN-code: 8733-3345

Researcher, Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1

Yulia K. Biryukova

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: biriukova-ula@mail.ru
ORCID iD: 0000-0002-5804-4001
SPIN-code: 7940-9531
Scopus Author ID: 36028326200
ResearcherId: D-8577-2014

PhD (Biology), Senior Researcher, Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1

Nadezhda M Kolyasnikova

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: kolyasnikova_nm@chumakovs.su

PhD (Medicine), Leading Researcher, Head of Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1

Mikhail F. Vorovich

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute); Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russian Federation (Sechenov University)

Email: vorovich_mf@chumakovs.su

PhD (Biology), Leading Researcher, Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development, Associate Professor, Department of Organization and Research of Immunobiological Technologies

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1; 119991, Moscow, st Trubetskaya 8/2

Nikolai B. Pestov

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: pestov_nb@chumakovs.su

PhD (Chemistry), Leading Researcher, Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1

Aidar A. Ishmukhametov

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute); Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of Russian Federation (Sechenov University)

Email: ishmukhametov@chumakovs.su
SPIN-code: 2971-8228
Scopus Author ID: 57195034442

RAS Full Member, DSc (Medicine), Professor, General Director, Head of the Department of Organization and Research of Immunobiological Technologies

 

Russian Federation, 108819, Moscow, Settlement “Moskovskiy”, Village of Institute of Poliomyelitis, Premises 8, build. 1; 119991, Moscow, st Trubetskaya 8/2

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