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Vol 52(2018) N 3 p. 306-322; DOI 10.1134/S002689331803010X Full Text

O.V. Matveeva1*, G.V. Kochneva2,3, S.S. Zainutdinov2,3, G.V. Ilyinskaya4,5 , P.M. Chumakov6,7

Oncolytic Paramyxoviruses: Mechanism of Action, Preclinical and Clinical Studies

1Biopolymer Design LLC, Acton, Massachusetts, United States
2State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk oblast, 630559 Russia
3Novosibirsk State University, Novosibirsk, 630090 Russia
4Russian Research Center of Medical Rehabilitation and Balneology, Moscow, 121099 Russia
5Blokhin Cancer Research Center, Moscow, 115478 Russia
6Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
7Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, Moscow, 108819 Russia

*Olga.Matveeva@gmail.com
Received - 2017-05-21; Accepted - 2017-07-10

Preclinical studies demonstrate that a broad spectrum of human and animal malignant cells can be killed by oncolytic paramyxoviruses, which includes cells of ecto-, endo- and mesodermal origin. In clinical trials, significant reduction or even complete elimination of primary tumors and established metastases has been reported. Different routes of virus administration (intratumoral, intravenous, intradermal, intraperito-neal, or intrapleural) and single- vs. multiple-dose administration schemes have been explored. The reported side effects were grades 1 and 2, with the most common among them being mild fever. There are certain advantages in using paramyxoviruses as oncolytic agents compared to members of other virus families exist. Thanks to cytoplasmic replication, paramyxoviruses do not integrate the host genome or engage in recombination, which makes them safer and more attractive candidates for widely used therapeutic oncolysis than ret-roviruses or some DNA viruses. The list of oncolytic Paramyxoviridae members includes the attenuated measles virus, mumps virus, low pathogenic Newcastle disease, and Sendai viruses. Metastatic cancer cells frequently overexpress certain surface molecules that can serve as receptors for oncolytic paramyxoviruses. This promotes specific viral attachment to these malignant cells. Paramyxoviruses are capable of inducing efficient syncytium-mediated lysis of cancer cells and elicit strong immune stimulation, which dramatically enforces anticancer immune surveillance. In general, preclinical studies and phases I-III of clinical trials yield very encouraging results and warrant continued research of oncolytic paramyxoviruses as a particularly valuable addition to the existing panel of cancer-fighting approaches.

oncolytic paramyxoviruses, viral oncolysis, Newcastle disease virus, vaccine strain of measles virus, Sendai virus, mumps virus, anticancer mechanism, anticancer immunity, cancer therapy, therapy of malignant tumors



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