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

封面

如何引用文章

全文:

详细

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.

作者简介

Alina Nazarenko

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: nazarenko_as@chumakovs.su
ORCID iD: 0000-0002-7322-8730

Junior researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

俄罗斯联邦, 108819, Moscow

Yulia Biryukova

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

编辑信件的主要联系方式.
Email: biryukova_jk@chumakovs.su
ORCID iD: 0000-0002-5804-4001

Ph. D., Researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), 108819, Russian Federation, Moscow. Russia

俄罗斯联邦, 108819, Moscow

Ekaterina Orlova

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: orlova_ea@chumakovs.su
ORCID iD: 0009-0009-4175-0493

Junior researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

俄罗斯联邦, 108819, Moscow

Kirill Trachuk

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: trachuk_kn@chumakovs.su
ORCID iD: 0000-0002-2061-0274

Junior researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia

俄罗斯联邦, 108819, Moscow

Alla Ivanova

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: ivanova_al@chumakovs.su
ORCID iD: 0009-0002-3086-0581

Ph. D., Microbiologist, Encephalitis Vaccine department, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

俄罗斯联邦, 108819, Moscow

Alla Belyakova

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: belyakova_av@chumakovs.su
ORCID iD: 0000-0003-4363-6394

Ph. D., Scientific secretary, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

俄罗斯联邦, 108819, Moscow

Nikolai Pestov

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: nayeoff@yahoo.com
ORCID iD: 0000-0002-9973-0120

Ph. D., Senior Researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia

俄罗斯联邦, 108819, Moscow

Mikhail Vorovitch

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis); I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Institute of Translational Medicine and Biotechnology

Email: vorovich_mf@chumakovs.su
ORCID iD: 0000-0002-7367-6357

Ph. D., Head of Encephalitis Vaccine Department and Senior Researcher of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

108819, Moscow; 119048, Moscow

Aydar Ishmukhametov

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis); I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Institute of Translational Medicine and Biotechnology

Email: ishmukhametov@chumakovs.su
ORCID iD: 0000-0001-6130-4145

Academician of the Russian Academy of Sciences, CEO, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow. Russia

俄罗斯联邦, 108819, Moscow; 119048, Moscow

Nadezhda Kolyasnikova

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis)

Email: kolyasnikova_nm@chumakovs.su
ORCID iD: 0000-0002-9934-2582

D.M.S, Head of the Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia

俄罗斯联邦, 108819, Moscow

参考

  1. Klaan N.K., Akin’shina L.P., Pronina T.A. Oncolitical viruses in the therapy of malignant neoplastic diseases. Rossiyskiy bioterapevticheskiy zhurnal. 2018; 17(4): 6–19. https://doi.org/10.17650/1726-9784-2018-17-4-6-19 https://elibrary.ru/ysbnsh (in Russian)
  2. Li K., Zhao Y., Hu X., Jiao J., Wang W., Yao H. Advances in the clinical development of oncolytic viruses. Am. J. Transl. Res. 2022; 14(6): 4192–206.
  3. Macedo N., Miller D.M., Haq R., Kaufman H.L. Clinical landscape of oncolytic virus research in 2020. J. Immunother. Cancer. 2020; 8(2): e001486. https://doi.org/10.1136/jitc-2020-001486
  4. Kolyasnikova N.M., Pestov N.B., Sanchez-Pimentel J.P., Barlev N.A., Ishmukhametov A.A. Anti-cancer virotherapy in Russia: lessons from the past, current challenges and prospects for the future. Curr. Pharm. Biotechnol. 2023; 24(2): 266–78. https://doi.org/10.2174/1389201023666220516121813
  5. Tsypkin L.B., Voroshilova M.K., Goryunova A.G., Lavrova I.K., Koroleva G.A. The morphology of tumors of the human gastrointestinal tract in short-term organ culture and the reaction of these tumors to infection with poliovirus. Cancer. 1976; 38(4): 1796–806. https://doi.org/10.1002/1097-0142(197610)38:4%3C1796::aid-cncr2820380457%3E3.0.co;2-y
  6. Voroshilova M.K., Goryuniva A.G., Gorbachkov E.A., Chumakov P.M., Oganian T.G., Kodkind G.H. Studies on Cellular Immunity of Oncology Patients in the Process of Asymptomic Enteroviral Infection. Riga: Zinātne; 1977: 17–20.
  7. Voroshilova M.K., Vaganova N.T. Treatment of Patients with Gastro-Intestinal Tract Tumors with Live Enteroviral Vaccines. Riga: Zinātne; 1969.
  8. Soboleva A.V., Lipatova A.V., Kochetkov D.V., Chumakov P.M. Changes in the sensitivity of human glioblastoma cells to oncolytic enteroviruses induced by passaging. Vestnik Rossiyskogo gosudarstvennogo meditsinskogo universiteta. 2018; (2): 40–4. https://doi.org/10.24075/brsmu.2018.025 https://elibrary.ru/uutsjs
  9. Sosnovtseva A.O., Chekhonin V.P., Zheltukhin A.O., Lipatova A.V., Chumakov P.M. Oncolytic activity of the vaccine strain of type 3 poliovirus on the model of rat glioma C6 cells. Byulleten’ eksperimental’noy biologii i meditsiny. 2019; 167(1): 111–5. https://doi.org/10.1007/s10517-019-04472-6 https://elibrary.ru/rrdykv
  10. Zheltukhin A.O., Soboleva A.V., Sosnovtseva A.O., Le T.Kh., Il’inskaya G.V., Kochetkov D.V., et al. Human enteroviruses exhibit selective oncolytic activity in the model of human glioblastoma multiforme xenografts in immunodeficient mice. Vestnik Rossiyskogo gosudarstvennogo meditsinskogo universiteta. 2018; (2): 42–8. https://doi.org/10.24075/brsmu.2018.026 https://elibrary.ru/xuagdz
  11. Stepanenko A.A., Sosnovtseva A.O., Valikhov M.P., Chekhonin V.P. A new insight into aggregation of oncolytic adenovirus Ad5-delta-24-RGD during CsCl gradient ultracentrifugation. Sci. Rep. 2021; 11(1): 16088. https://doi.org/10.1038/s41598-021-94573-y
  12. Romanenko M.V., Dolgova E.V., Osipov I.D., Ritter G.S., Sizova M.S., Proskurina A.S., et al. Oncolytic effect of adenoviruses serotypes 5 and 6 against U87 glioblastoma cancer stem cells. Anticancer Res. 2019; 39(11): 6073–86. https://doi.org/10.21873/anticanres.13815
  13. Svyatchenko V.A., Netesov S.V., Tarasova M.V., Chumakov P.M. Oncolytic adenoviruses in anticancer therapy: current status and prospects. Molekulyarnaya biologiya. 2012; (4): 496–507. https://doi.org/10.1134/S0026893312040103 https://elibrary.ru/rgfvkf
  14. Vdovochenko G.V., Radaeva I.F., Sergeev A.A., Kolokol’tsova T.D., Nechaeva E.A., Il’ina T.V., et al. Development of banks of a 203-cell continuous culture for manufacturing the anti-tumor therapeutic preparation cancerolysin. Biotekhnologiya. 2006; (1): 83–9. https://elibrary.ru/iiqmwx
  15. Vdovichenko G.V., Petrishchenko V.A., Sergeyev A.A., Kim I.I., Fatyukhina O.Ye., Shishkina L.N., et al. Preclinical studies of the anticancer adenovirus cancerolysin. Voprosy virusologii. 2006; 51(6): 39–42. https://elibrary.ru/hylfpr (in Russian)
  16. Vdovichenko G.D., Petrishchenko V.A., Sergeev A.A., Kim I.I., Fatyukhina O.E., Shishkina L.N., et al. Study on reactogenicity, safety and specific activity of an anticancer medicinal preparation cancerolysin using test animals. Biotekhnologiya. 2006; (2): 88–96. https://elibrary.ru/ibjlpf
  17. Bauer T.V., Tregubchak T.V., Maksyutov A.Z., Taranov O.S., Maksyutov R.A., Gavrilova E.V., et al. Recombinant vaccinia virus promising for melanoma treatment. Molekulyarnaya genetika, mikrobiologiya i virusologiya. 2020; 35(2): 97–104. https://doi.org/10.3103/S0891416820020032 https://elibrary.ru/ujwwtp
  18. Nazarenko A.S., Vorovitch M.F., Biryukova Y.K., Pestov N.B., Orlova E.A., Barlev N.A., et al. Flaviviruses in antitumor therapy. Viruses. 2023; 15(10): 1973. https://doi.org/10.3390/v15101973
  19. Lemos de Matos A., Franco L.S., McFadden G. Oncolytic viruses and the immune system: the dynamic duo. Mol. Ther. Methods Clin. Dev. 2020; 17: 349–58. https://doi.org/10.1016/j.omtm.2020.01.001
  20. Postler T.S., Beer M., Blitvich B.J., Bukh J., de Lamballerie X., Drexler J.F., et al. Renaming of the genus flavivirus to orthoflavivirus and extension of binomial species names within the family flaviviridae. Arch. Virol. 2023; 168(9): 224. https://doi.org/10.1007/s00705-023-05835-1
  21. Zhu Z., Gorman M.J., McKenzie L.D., Chai J.N., Hubert C.G., Prager B.C., et al. Zika virus has oncolytic activity against glioblastoma stem cells. J. Exp. Med. 2017; 214(10): 2843–57. https://doi.org/10.1084/jem.20171093
  22. Svyatchenko V.A., Razumov I.A., Protopopova E.V., Demina A.M., Solovieva O.I., Zavjalov E.L., et al. Zika virus has an oncolytic activity against human glioblastoma U87 cells. Vavilovskiy zhurnal genetiki i selektsii. 2019; 22(8): 1040–5. https://doi.org/10.18699/VJ18.448 https://elibrary.ru/yqnnul (in Russian)
  23. Monath T.P., Vasconcelos P.F. Yellow fever. J. Clin. Virol. 2015; 64: 160–73. https://doi.org/10.1016/j.jcv.2014.08.030
  24. Zhu X., Fan C., Xiong Z., Chen M., Li Z., Tao T., et al. Development and application of oncolytic viruses as the nemesis of tumor cells. Front. Microbiol. 2023; 14: 1188526. https://doi.org/10.3389/fmicb.2023.1188526
  25. Aznar M.A., Molina C., Teijeira A., Rodriguez I., Azpilikueta A., Garasa S., et al. Repurposing the yellow fever vaccine for intratumoral immunotherapy. EMBO Mol. Med. 2020; 12(1): e10375. https://doi.org/10.15252/emmm.201910375
  26. Levkovich E.N., Karpovich L.G. Comparative study of the viruses of the tick encephalitis group in HeLa cell cultures. Voprosy virusologii. 1960; (5): 30–9. (in Russian)
  27. Levkovich E.N., Sergeeva G.I. The inhibiting effect of tick-borne encephalitis complex viruses possessing varying neurovirulence on mouse tumors in vivo. Byulleten’ eksperimental’noy biologii i meditsiny. 1967; 64(8): 88–91. (in Russian)
  28. Sergeeva G.I., Levkovich E.N. A study of the features of reproduction in tumor cells in vitro and in vivo of different viruses of the tick-borne encephalitis complex, possessing various degress of neurovirulence. Voprosy virusologii. 1966; 11(5): 539–45. (in Russian)
  29. Koudan E.V., Gryadunova A.A., Karalkin P.A., Korneva J.V., Meteleva N.Y., Babichenko I.I., et al. Multiparametric analysis of tissue spheroids fabricated from different types of cells. Biotechnol. J. 2020; 15(5): 1900217. https://doi.org/10.1002/biot.201900217
  30. Dutta S.K., Langenburg T. A perspective on current flavivirus vaccine development: a brief review. Viruses. 2023; 15(4): 860. https://doi.org/10.3390/v15040860
  31. Lindquist L., Vapalahti O. Tick-borne encephalitis. Lancet. 2008; 371(9627): 1861–71. https://doi.org/10.1016/s0140-6736(08)60800-4
  32. Moore A.E. The destructive effect of the virus of Russian Far East encephalitis on the transplantable mouse sarcoma 180. Cancer. 1949; 2(3): 525–34. https://doi.org/10.1002/1097-0142(194905)2:3%3C525::aid-cncr2820020317%3E3.0.co;2-o
  33. Moore A.E. Inhibition of growth of five transplantable mouse tumors by the virus of Russian Far East encephalitis. Cancer. 1951; 4(2): 375–82. https://doi.org/10.1002/1097-0142(195103)4:2%3C375::aid-cncr2820040227%3E3.0.co;2-a
  34. Chiantore M.V., Mangino G., Zangrillo M.S., Iuliano M., Affabris E., Fiorucci G., et al. Role of the Microenvironment in tumourigenesis: focus on virus-induced tumors. Curr. Med. Chem. 2015; 22(8): 958–74. https://doi.org/10.2174/0929867322666141212121751
  35. Gál P., Varinská L., Fáber L., Novák Š., Szabo P., Mitrengová P., et al. How signaling molecules regulate tumor microenvironment: parallels to wound repair. Molecules. 2017; 22(11): 1818. https://doi.org/10.3390/molecules22111818
  36. Lipatova A.V., Soboleva A.V., Gorshkov V.A., Bubis J.A., Solovyeva E.M., Krasnov G.S., et al. Multi-omics analysis of glioblastoma cells’ sensitivity to oncolytic viruses. Cancers (Basel). 2021; 13(21): 5268. https://doi.org/10.3390/cancers13215268
  37. Moerdyk-Schauwecker M., Shah N.R., Murphy A.M., Hastie E., Mukherjee P., Grdzelishvili V.Z. Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: role of type I interferon signaling. Virology. 2013; 436(1): 221–34. https://doi.org/10.1016/j.virol.2012.11.014
  38. Sakai T., Mashima H., Yamada Y., Goto T., Sato W., Dohmen T., et al. The roles of interferon regulatory factors 1 and 2 in the progression of human pancreatic cancer. Pancreas. 2014; 43(6): 909–16. https://doi.org/10.1097/mpa.0000000000000116

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Sensitivity of glioblastoma cells GL6, LN-229, T98G, pancreatic carcinoma MIA Paca-2 and pancreatic ductal carcinoma PANC-1 cell to strain 17D YFV (panel а) and strain Sofjin TBEV (panel b) depending on the virus titer at the infection as assessed by the proportion of surviving cells using the MTT test at 5 days post-infection. Photographs of MIA Paca-2 cells. Magnification ×100. а(1) – control well, monolayer preserved; а(2) – infected well, complete cell lysis.

下载 (283KB)
索引源数据
3. Fig. 2. Changes in viral RNA concentration in the culture medium following infection (day 0) of GL6, LN-229, T98G glioblastomas with strain 17D YFV on days 3, 5, 7, 10, 13 of the experiment.

下载 (274KB)
索引源数据
4. Fig. 3. Changes in viral RNA concentration in the culture medium following infection (day 0) of GL6, LN-229, T98G glioblastomas strain Sofjin TBEV on days 3, 5, 7, 10, 13 of the experiment.

下载 (266KB)
索引源数据
5. Fig. 4. Assessment of the CPE of 17D YFV using tissue spheroids on MIA Paca-2 cell culture. The photo shows the view of spheroids at 3 days control – uninfected spheroid (panel а) and after infection with 106 MOI/ml strain 17D YFV – (panel b). Magnification × 40.

下载 (713KB)
索引源数据

版权所有 © Nazarenko A.S., Biryukova Y.K., Orlova E.O., Trachuk K.N., Ivanova A.L., Belyakova A.V., Pestov N.B., Vorovitch M.F., Ishmukhametov A.A., Kolyasnikova N.M., 2023

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».