Потенциал использования онколитических вирусов при раке молочной железы: исторические аспекты и будущие перспективы (обзор литературы)

Морозов Д.А., Колядина И.В., Поддубная И.В. и др. Потенциал использования онколитических вирусов при раке молочной железы: исторические аспекты и будущие перспективы (обзор литературы). Современная Онкология. 2019; 21 (1): 31–35. DOI: 10.26442/18151434.2019.1.190299

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Morozov D.A., Kolyadina I.V., Poddubnaya I.V. et al. The potential use of oncolytic viruses in breast cancer: historical aspects and future prospects (literature review). Journal of Modern Oncology. 2019; 21 (1): 31–35. DOI: 10.26442/18151434.2019.1.190299

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Аннотация

Вирусный онколизис, подход к терапии онкологических заболеваний, возникший в XX в. и основанный на естественной способности вирусов убивать (лизировать) клетки, в которых он размножается, свое развитие получил в последние годы благодаря выявлению вирусов или их инженерных вариантов с избирательной опухолевой репликацией. За последние десятилетия описан ряд специфических взаимодействий онколитических вирусов – ОВ (как РНК-, так и ДНК-содержащих) с клетками злокачественных опухолей, выявлены отдельные вирусы-кандидаты и лизируемые ими типы опухолей. Терапевтическая эффективность ОВ достигается за счет комбинации селективного уничтожения опухолевых клеток посредством прямого цитотоксического эффекта и активации противоопухолевого иммунитета; кроме того, ОВ могут влиять на абберантные сигнальные пути с последующей блокадой апоптоза опухолевой клетки, что дает вирусу больше времени для завершения своего жизненного цикла. Ряд ОВ показали многообещающую терапевтическую эффективность в доклинических исследованиях при раке молочной железы; так, вирус простого герпеса обладает высокой селективностью к репликации в опухолевых клетках, что способствует гибели и образованию инфильтрации CD8+ и CD4+ Т-клеток вокруг опухолевых островков. Обнаружена способность реовирусов усиливать экспрессию в клетках белка PD-L1, а вирус кори, вооруженный геном проапоптоза BNiP3, более активен в клеточных линиях тройного негативного рака молочной железы. Улучшенные вирусы с точки зрения эффективности и селективности воздействия на опухоль, а также оптимизированные комбинации с другими «стандартными» видами системной терапии представляются весьма перспективными, особенно у больных с развившейся лекарственной резистентностью.

Ключевые слова: рак молочной железы, резистентность к лекарственной терапии, онколитические вирусы, механизмы онколизиса ДНК- и РНК-содержащих вирусов, тройной негативный рак.

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Viral oncolysis, an approach to cancer therapy that emerged in the XX century and based on the natural ability of viruses to kill (lyse) cells in which it multiplies, has been developed in recent years by identifying viruses or their engineering variants with selective tumor replication. Over the past decades, a number of specific interactions of oncolytic viruses (both RNA and IDNA-containing) with malignant tumor cells have been described, individual candidate viruses and the types of tumors that they lase have been detected. The therapeutic efficacy of oncolytic viruses is achieved through a combination of selective destruction of tumor cells through a direct cytotoxic effect and activation of antitumor immunity; In addition, oncolytic viruses can affect abberant signaling pathways followed by blockade of tumor cell apoptosis, which gives the virus more time to complete its life cycle. A number of oncolytic viruses have shown promising therapeutic efficacy in preclinical studies in breast cancer; thus, the herpes simplex virus has a high selectivity for replication in tumor cells, which contributes to the death and the formation of infiltration of CD8+ and CD4+ T cells around tumor islands. The ability of reoviruses to enhance the expression of PD-L1 protein in cells was found, and the measles virus armed with the BNiP3 proapoptosis gene is more active in the cell lines of triple negative breast cancer. Improved viruses, from the point of view of the effectiveness and selectivity of effects on the tumor, as well as optimized combinations with other "standard" types of systemic therapy, are very promising, especially in patients with developed drug resistance.

Key words: breast cancer, resistance to systemic therapy therapy, oncolytic viruses, oncolysis mechanisms of DNA and RNA viruses, triple negative cancer.

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Список литературы

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23. Ahmed A. Mostafa, Meyers DE et al. Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer. Cancers 2018; 10: 205.
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1. Netesov S.V., Kochneva G.V., Loktev V.B. et al. Onkoliticheskie virusy: dostizheniia i problemy. Meditsinskii alfavit. Epidemiologiia i sanitariia. 2011; 3: 26–33 (in Russian).
2. Lawler S, Speranza M, Cho Ch et al. Oncolytic Viruses in Cancer Treatment A Review JAMA Oncol 2017; 3 (6): 841–9.
3. Voroshilova M.K. Poleznye dlia organizma nepatogennye shtammy enterovirusov: profilakticheskoe i lechebnoe ikh primenenie. Moscow, 1988; s. 24–9 (in Russian).
4. Martuza RL et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 1991; 252: 854–6.
5. Advances in the mechanisms of action of cancer targeting oncolytic viruses. Oncology Letters 2018; 15: 4053–60.
6. Takeda K, Akira S. Toll‐Like Receptors. Curr Protoc Immunol 2015; 109: 14.12.1– 14.12.10.
7. Moanaro Biswas, Sandeep R.P. Kumar, Adria Allen et al. Cell-Type-Speciﬁc Innate Immune Responseto Oncolytic Newcastle Disease Virus. Viral Immunology 2012; 25 (4): 268–76.
8. Inoue H, Tani K. Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments. Cell death and differentiation 2013; 21 (1): 39–49.
9. Pestka S, Langer JA, Zoon KC, Samuel CE. Interferons and their actions. Ann Rev Biochem 1987; 56: 727.
10. Pikor LA, Bell JC, Diallo J-S. Oncolytic Viruses: Exploiting Cancer's Deal with the Devil. Trends in Cancer 2015; 1 (4).
11. Yu W, Fang H. Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets 2007; 7 (2): 141–8.
12. Kuhn I, Harden P, Bauzon M et al. Directed evolution generates a novel oncolytic virus for the treatment of colon cancer. PLoS One 2008.
13. Ranki T, Kanerva, A, Ristimäki A et al. A heparan sulfate-targeted conditionally replicative adenovirus, Ad5.pk7-Delta24, for the treatment of advanced breast cancer. Gene Ther 2006; 14 (1): 58–67.
14. Murphy AM, Rabkin SD. Current status of gene therapy for brain tumors. Translational research. J Lab Clin Med 2012; 161 (4): 339–54.
15. Smakman N et al. KRAS (D13) Promotes apoptosis of human colorectal tumor cells by ReovirusT3D and oxaliplatin but not by tumor necrosis factor-related apoptosisinducing ligand. Cancer Res 2006; 66 (10): 5403–8.
16. Brown MC, Dobrikova EY, Dobrikov MI et al. Oncolytic polio virotherapy of cancer. Cancer 2014; 120 (21): 3277–86.
17. Brown MC, Gromeier M. Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus. Curr Opin Virol 2015; 13: 81–5.
18. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66: 7–30.
19. Kolyadina I.V., Andreeva Iu.Iu., Frank G.A., Poddubnaia I.V. Rol' biologicheskoi geterogennosti pri retsidiviruiushchem i metastaticheskom rake molochnoi zhelezy. Arkhiv patologii. 2018; 80 (6): 62–7 (in Russian).
20. Kolyadina I.V., Poddubnaya I.V. The role of capecitabine and eribulin in the treatment of metastatic HER2-negative metastatic breast cancer. Journal of Modern Oncology. 2018; 20 (3): 26–29. DOI: 10.26442/1815-1434_2018.3.26-29 (in Russian).
21. Eissa I, Bustos-Villalobos I, Ichinose T et al. The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers. Cancers 2018; 10: 356. DOI: 10.3390/cancers10100356
22. Nakao A, Kimata H, Imai T et al. Intratumoral Injection of Herpes Simplex Virus HF10 in Recurrent Breast Cancer. Ann Oncol 2004; 15: 988–9.
23. Ahmed A. Mostafa, Meyers DE et al. Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer. Cancers 2018; 10: 205.
24. Shashi Gujara, Jonathan G. Pol, Guido Kroemer. Heating it up: Oncolytic viruses make tumors ‘hot’ and suitable for checkpoint blockade immunotherapies. Oncoimmunology 2018; 7 (8).
25. Gollamudi R, Ghalib MH, Desai KK et al. Intravenous Administration of Reolysin®, a Live Replication Competent RNA Virus is Safe in Patients with Advanced Solid Tumors. Invest New Drugs 2010; 28: 641–9.
26. Bernstein V, Ellard SL, Dent SF et al. A Randomized Phase II Study of Weekly Paclitaxel with or without Pelareorep in Patients with Metastatic Breast Cancer: Final Analysis of Canadian Cancer Trials Group IND. 213. Breast Cancer Res Treat 2018; 167: 485–93.
27. Lal G, Rajala MS. Combination of Oncolytic Measles Virus Armed With BNiP3, a Pro-apoptotic Gene and Paclitaxel Induces Breast Cancer Cell Death. Front Oncol 2019; 8: 676.
28. Martin NT, Roy DG, Workenhe ST et al. Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer. Scientific Reports 2019; 9: 1865.

Авторы

Д.А.Морозов1,2, И.В.Колядина*1,2, И.В.Поддубная1,2, П.М.Чумаков3, Г.В.Ильинская3, В.Ю.Бохян2, М.И.Сопова4

1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23;
3 ФГБУ «Институт молекулярной биологии им. В.А.Энгельгардта» РАН. 119991, Россия, Москва, ул. Вавилова, д. 32;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 2
*irinakolyadina@yandex.ru

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Dmitriy A. Morozov1,2, Irina V. Kolyadina*1,2, Irina V. Poddubnaya1,2, Petr M. Chumakov3, Galina V. Ilinskaya3, Vagan Yu. Bokhian2, Margarita I. Sopova4

1 Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 2/1, Barrikadnaia st., Moscow, 125993, Russian Federation;
2 N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 23, Kashirskoe h., Moscow, 115478, Russian Federation;
3 V.A.Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences. 32, Vavilova st., Moscow, 119991, Russian Federation;
4 I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 8, bld. 2, Trubetskaia st., Moscow, 119991, Russian Federation
*irinakolyadina@yandex.ru

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