Современные подходы к онколитической иммуновиротерапии онкологических заболеваний на основе энтеровирусов

Цель. Представить обзор современных подходов к онколитической вироиммунотерапии онкологических заболеваний с применением энтеровирусов по данным мировой научной литературы.

Материалы и методы. Для сбора и анализа сведений использованы электронные базы данных PubMed, Scopus, Web of Science, Google Scholar, библиотечная база данных (eLibrary.ru) и другие доступные ресурсы. Поиск проведён по публикациям за 1990–2024 гг. по ключевым словам: «онколитическая виротерапия», «онколитические вирусы», «энтеровирусы», «poliovirus», «coxsackievirus», «echovirus», «доклинические исследования», «клинические испытания».

Результаты. Представлены данные о свойствах онколитических вирусов дикого типа и геномодифицированных вирусов, на которых основан выбор вируса для разработки лекарственного препарата, и о механизмах их действия. Они включают прямое цитолитическое действие, обусловленное внутриклеточным размножением вируса; активацию противоопухолевого иммунитета организма — реципиента вируса за счет презентации опухоль-ассоциированных антигенов дендритным клеткам с последующим их созреванием, презентацией антигенов Т-лимфоцитам и активацией цитотоксических лимфоцитов; модуляцию опухолевого микроокружения окружения в результате иммуностимуляции и перехода «холодной» опухоли и окружающей ткани в «горячее» состояние. Отмечено, что наиболее выраженный терапевтический эффект наблюдается в отношении иммуночувствительных опухолей, что коррелирует с механизмом действия онколитических вирусов. Клинические испытания лекарственных препаратов пока не привели к прорывным результатам по терапевтическому действию, но показали синергизм по эффективности с другими видами консервативной терапии. По результатам доклинических и клинических исследований, энтеровирусы проявляют благоприятный профиль токсичности. Оценены факторы, снижающие эффективность виротерапии: недостаточно целенаправленное попадание вируса в опухолевые клетки, неактивный эндоцитоз и размножение с последующим распространением в организме; предсуществующий в организме иммунитет против конкретного вируса и индукция выработки антител к нему в процессе виротерапии; отсутствие чувствительности самой опухоли и ее микроокружения к вирусу.

Заключение. Онколитическая виротерапия на основе энтеровирусов перспективна, но эффективность ее необходимо повышать, опираясь на механизмы действия.

1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries // CA Cancer J Clin. – 2021. – Vol. 71, No. 3. – P. 209–249. DOI: 10.3322/caac.21660

2. Состояние онкологической помощи населению России в 2024 году. Ред. А.Д. Каприн, В.В. Старинский, А.О. Шахзадова. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России. – 2025. – 275 с. ISBN 978-5-85502-309-1

3. Yi M., Li T., Niu M., Mei Q., Zhao B., Chu Q., Dai Z., Wu K. Exploiting innate immunity for cancer immunotherapy // Molecular Cancer. – 2023. – Vol. 22, No. 1. – P. 187–242. DOI: 10.1186/s12943-023-01885-w

4. Chen D.S., Mellman I. Oncology Meets Immunology: The Cancer–Immunity Cycle // Immunity. – 2013. – Vol. 39, No. 1. – P. 1–10. DOI: 10.1016/j.immuni.2013.07.012

5. Wang W., Liu S., Dai P., Yang N., Wang Y., Giese RA., Merghoub T., Wolchok J., Deng L. Elucidating mechanisms of antitumor immunity mediated by live oncolytic vaccinia and heat–inactivated vaccinia // J Immuno Ther Cancer. – 2021. – Vol. 9, No. 9. – P. e002569. DOI: 10.1136/jitc-2021-002569

6. Kamil F., Rowe J.H. How does the tumor microenvironment play a role in hepatobiliary tumors? // J Gastrointest Oncol. – 2018. – Vol. 9, No. 1. – P. 180–195. DOI: 10.21037/jgo.201706.09

7. Ylä-Pelto J., Tripathi L., Susi P. Therapeutic use of native and recombinant enteroviruses // Viruses. – 2016. – Vol. 8, No. 3. – P. 57–72. DOI: 10.3390/v8030057

8. Bejarano L., Jordão M.J.C., Joyce J.A. Therapeutic targeting of the tumor microenvironment // Cancer Discov. – 2021. – Vol. 11, No. 4. – P. 933–959. DOI: 10.1158/2159-8290.CD-20-1808

9. Wang L., Chard Dunmall L.S., Cheng Z., Wang Y. Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment // J Immunother Cancer. – 2022. – Vol. 10, No. 5. – P. e004167. DOI: 10.1136/jitc-2021-004167

10. Volovat S.R., Scripcariu D.V., Vasilache I.A., Stolniceanu C.R., Volovat C., Augustin I.G., Volovat C.C., Ostafe M.R., Andreea-Voichița S.G., Bejusca-Vieriu T., Lungulescu C.V., Sur D., Boboc D. Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy // Int J Mol Sci. 2024. – Vol. 25, No. 2. – P. 1180. DOI: 10.3390/ijms25021180

11. Hemminki O., Dos Santos J.M., Hemminki A. Oncolytic viruses for cancer immunotherapy // J Hematol Oncol. – 2020. – Vol. 13, No. 1. – P. 84. DOI: 10.1186/s13045-020-00922-1

12. Rahman M.M., McFadden G. Oncolytic viruses: Newest Frontier for Cancer Immunotherapy // Cancers. – 2021. – Vol. 13, No. 21. – P. 5452. DOI: 10.3390/cancers13215452

13. Harrington K., Freeman D.J., Kelly B., Harper J., Soria J.C. Optimizing oncolytic virotherapy in cancer treatment // Nat Rev Drug Discov. – 2019. – Vol. 18, No. 9. – P. 689–706. DOI: 10.1038/s41573-019-0029-0

14. Lawler S.E., Speranza M.C., Cho C.F., Chiocca E.A. Oncolytic viruses in cancer treatment: a Review // JAMA Oncol. – 2017. – Vol. 3, No. 6. – P. 841849. DOI: 10.1001/jamaoncol.2016.2064

15. Zainutdinov S.S., Kochneva G.V., Netesov S.V., Chumakov P.M., Matveeva O.V. Directed evolution as a tool for the selection of oncolytic RNA viruses with desired phenotypes // Oncolytic Virotherapy. – 2019. – Vol. 8. – P. 9–26. DOI: 10.2147/OV.S176523. eCollection 2019

16. Engeland C.E., Ungerechts G. Measles virus as an oncolytic immunotherapy // Cancers. – 2021. – Vol. 13, No. 3. – P. 544. DOI: 10.3390/cancers13030544

17. Lin L.T., Richardson C.D. The host cell receptors for measles virus and their interaction with the viral hemagglutinin (H) protein // Viruses. – 2016. – Vol. 8, No. 9. – P. 250. DOI: 10.3390/v8090250

18. He Y., Mueller S., Chipman P.R., Bator C.M., Peng X., Bowman V.D., Mukhopadhyay S., Wimmer E., Kuhn R.J., Rossmann M.G. Complexes of poliovirus serotypes with their common cellular receptor, CD155 // J Virol. – 2003. – Vol. 77, No. 8. – P. 4827–4835. DOI: 10.1128/jvi.77.8.4827-4835.2003

19. Bergelson J.M., Shepley M.P., Chan B.M., Hemler M.E., Finberg R.W. Identification of the integrin VLA-2 as a receptor for echovirus 1 // Science. – 1992. – Vol. 255, No. 5052. – P. 1718–1720. DOI: 10.1126/science.1553561

20. Rahman MM., McFadden G. Oncolytic virotherapy with Myxoma virus // J Clin Med. – 2020. – Vol. 9, No. 1. – P. 171. DOI: 10.3390/jcm9010171

21. Rahman M.M., McFadden G. Myxoma virus-encoded host range protein M029: a multifunctional antagonist targeting multiple host antiviral and innate immune pathways // Vaccines. – 2020. – Vol. 8, No. 2. – P. 244. DOI: 10.3390/vaccines8020244

22. Matveeva O.V., Chumakov P.M. Defects in interferon pathways as potential biomarkers of sensitivity to oncolytic viruses // Rev Med Virol. – 2018. – Vol. 28. – P. e2008. DOI: 10.1002/rmv.2008

23. Cai J., Zhu W., Lin Y., Hu J., Liu X., Xu W., Liu Y., Hu C., He S., Gong S., Yan G., Liang J. Lonidamine potentiates the oncolytic efficiency of M1 virus independent of hexokinase 2 but via inhibition of antiviral immunity // Cancer Cell Int. – 2020. – Vol. 20, No. 1. – P. 532. DOI: 10.1186/s12935-020-01598-w

24. Garant K.A., Shmulevitz M., Pan I., Daigle R.M., Ahn D.G., Gujar S.A., Lee P.W.K. Oncolytic reovirus induces intracellular redistribution of RAS to promote apoptosis and progeny virus release // Oncogene. – 2016. – Vol. 35, No. 6. – P. 771–782. DOI: 10.1038/onc.2015.136

25. Pol J.G., Workenhe S.T., Konda P., Gujar S., Kroemer G. Cytokines in oncolytic virotherapy // Cytokine Growth Factor Rev. – 2020. – Vol. 56:4–27. DOI: 10.1016/j.cytogfr.2020.10.007

26. Borrego-Diaz E., Mathew R., Hawkinson D., Esfandyari T., Liu Z., Lee P.W., Farassati F. Pro-oncogenic cell signaling machinery as a target for oncolytic viruses // Curr Pharm Biotechnol. – 2012. – Vol. 13, No. 9. – P. 1742–1749. DOI: 10.2174/138920112800958788

27. Conner J., Braidwood L., Brown S.M. A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein // Gene Ther. – 2008. – Vol. 15, No. 24. – P. 1579–1592. DOI: 10.1038/gt.2008.121

28. Howells A., Marelli G., Lemoine N.R., Wang Y. Oncolytic viruses – interaction of virus and tumor cells in the battle to eliminate cancer // Front Oncol. – 2017. – Vol. 7. – P. 195. DOI: 10.3389/fonc.2017.00195

29. Seegers S.L., Frasier C., Greene S., Nesmelova I.V., Grdzelishvili V.Z. Experimental evolution generates novel oncolytic vesicular stomatitis viruses with improved replication in virus-resistant pancreatic cancer cells // J Virol. – 2020. – Vol. 94, No. 3. – P. e01643-19. DOI: 10.1128/JVI.01643-19

30. Uche I.K., Kousoulas K.G., Rider P.J.F. The effect of Herpes Simplex Virus-Type-1 (HSV-1) Oncolytic Immunotherapy on the Tumor Microenvironment // Viruses. – 2021. – Vol. 13, No. 7. – P. 1200. DOI: 10.3390/v13071200

31. Boagni D.A., Ravirala D., Zhang S.X. Current strategies in engaging oncolytic viruses with antitumor immunity // Mol Ther Oncolytics. – 2021. – Vol. 22. – P. 98–113. DOI: 10.1016/j.omto.2021.05.002

32. Imre G. Cell death signaling in virus infection // Cell Signal. – 2020. – Vol. 76. – Р. 109772. DOI: 10.1016/j.cellsig.2020.109772

33. Rex D.A.B., Prasad T.S.K., Kandasamy R.K. Revisiting Regulated Cell Death Responses in Viral Infections // Int. J. Mol. Sci. – 2022. – Vol. 23. – P. 7023. DOI: 10.3390/ijms23137023

34. Ahmed J., Chard L.S., Yuan M., Wang J., Howells A., Li Y., Li H., Zhang Z., Lu S., Gao D., Wang P., Chu Y., Al Yaghchi C., Schwartz J., Alusi G., Lemoine N., Wang Y. A new oncolytic V vaccinia virus augments antitumor immune responses to prevent tumor recurrence and metastasis after surgery // J Immunother Cancer. – 2020. – Vol. 8, No. 1. – P. e000415. DOI: 10.1136/jitc-2019-000415

35. Prestwich R.J., Harrington K.J., Pandha H.S., Vile R., Melcher A.A., Errington F. Oncolytic viruses: a novel form of immunotherapy // Expert Rev Anticancer Ther. – 2008. – Vol. 8, No. 10. – P. 1581–1588. DOI: 10.1586/14737140.8.10.1581

36. Malka D., Lièvre A., André T., Taïeb J., Ducreux M., Bibeau F. Immune scores in colorectal cancer: where are we? // Eur J Cancer. – 2020. – Vol. 140. – P. 105–118. DOI: 10.1016/j.ejca.2020.08.024

37. Guo Z.S., Liu Z., Bartlett D.L. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity // Front Oncol. – 2014. – Vol. 4. – P. 74. DOI: 10.3389/fonc.2014.00074

38. Laoui D., Keirsse J., Morias Y., Van Overmeire E., Geeraerts X., Elkrim Y., Kiss M., Bolli E., Lahmar Q., Sichien D., Serneels J., Scott CL., Boon L., De Baetselier P., Mazzone M., Guilliams M., Van Ginderachter JA. The tumor microenvironment harbors ontogenically distinct dendritic cell populations with opposing effects on tumor immunity // Nat Commun. – 2016. – Vol. 7. – P. 13720. DOI: 10.1038/ncomms13720

39. Nguyen H.M., Guz-Montgomery K., Saha D. Oncolytic virus encoding a master pro-inflammatory cytokine 12 in cancer immunotherapy // Cells. – 2020. – Vol. 9. – P. 400. DOI: 10.3390/cells9020400

40. Ghouse S.M., Nguyen H.M., Bommareddy P.K., Guz-Montgomery K., Saha D. Oncolytic herpes simplex virus encoding IL12 controls triple-negative breast cancer growth and metastasis // Front Oncol. – 2020. – Vol. 10. – P. 384. DOI: 10.3389/fonc.2020.00384

41. Yang M., Giehl E., Feng C., Feist M., Chen H., Dai E., Liu Z., Ma C., Ravindranathan R., Bartlett D.L., Lu B., Guo Z.S. IL-36γ-armed oncolytic virus exerts superior efficacy through induction of potent adaptive antitumor immunity // Cancer Immunol Immunother. – 2021. – Vol. 70, No. 9. – P. 2467–2481. DOI: 10.1007/s00262-021-02860-4

42. Jayasingam S.D., Citartan M., Thang T.H., Mat Zin A.A., Ang K.C., Ch’ng E.S. Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: Technicalities and challenges in routine clinical practice // Front Oncol. – 2020. – Vol. 9. – P. 1512. DOI: 10.3389/fonc.2019.01512

43. Kumar V., Giacomantonio M.A., Gujar S. Role of myeloid cells in oncolytic reovirus-based cancer therapy // Viruses. – 2021. – Vol. 13, No. 4. – P. 654. DOI: 10.3390/v13040654

44. Kwan A., Winder N., Atkinson E., Al-Janabi H., Allen RJ., Hughes R., Moamin M., Louie R., Evans D., Hutchinson M., Capper D., Cox K., Handley J., Wilshaw A., Kim T., Tazzyman SJ., Srivastava S., Ottewell P., Vadakekolathu J., Pockley G., Lewis CE., Brown J.E., Danson S.J., Conner J., Muthana M. Macrophages mediate the antitumor effects of the oncolytic virus HSV1716 in mammary tumors // Mol Cancer Ther. – 2021. – Vol. 20, No. 3. – P. 589–601. DOI: 10.1158/1535-7163.MCT-20-0748

45. El-Sherbiny Y.M., Holmes T.D., Wetherill L.F., Black E.V., Wilson E.B., Phillips S.L., Scott G.B., Adair R.A., Dave R., Scott K.J., Morgan R.S., Coffey M., Toogood G.J., Melcher A.A., Cook G.P. Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo // Clin Exp Immunol. – 2015. – Vol. 180, No. 1. – P. 98–107. DOI: 10.1111/cei.12562

46. Chouljenko D.V., Ding J., Lee I.F., Murad Y.M., Bu X., Liu G., Delwar Z., Sun Y., Yu S., Samudio I., Zhao R., Jia W.G. Induction of durable antitumor response by a novel oncolytic herpesvirus expressing multiple immunomodulatory transgenes // Biomedicines. – 2020. – Vol. 8, No. 11. – P. 484. DOI: 10.3390/biomedicines8110484

47. Li K., Shi H., Zhang B., Ou X., Ma Q., Chen Y., Shu P., Li D., Wang Y. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer // Signal Transduct Target Ther. – 2021. – Vol. 6, No. 1. – P. 362. DOI: 10.1038/s41392-021-00670-9

48. Katayama Y., Tachibana M., Kurisu N., Oya Y., Terasawa Y., Goda H., Kobiyama K., Ishii K.J., Akira S., Mizuguchi H., Sakurai F. Oncolytic reovirus inhibits immunosuppressive activity of myeloid-derived suppressor cells in a TLR3-dependent manner // J Immunol. – 2018. – Vol. 200, No. 8. – P. 2987–2999. DOI: 10.4049/jimmunol.1700435

49. Nguyen T.T., Shin D.H., Sohoni S., Singh S.K., Rivera-Molina Y., Jiang H., Fan X., Gumin J., Lang F.F., Alvarez-Breckenridge C., Godoy-Vitorino F., Zhu L., Zheng W.J., Zhai L., Ladomersky E., Lauing KL., Alonso M.M., Wainwright D.A., Gomez-Manzano C., Fueyo J. Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry // J Immunother Cancer. – 2022. – Vol. 10, No. 7. – P. e004935. DOI: 10.1136/ jitc-2022-004935

50. Ferguson M.S., Lemoine N.R., Wang Y. Systemic delivery of oncolytic viruses: hopes and hurdles // Adv Virol. – 2012. – Vol. 2012. – P. 805629. DOI: 10.1155/2012/805629

51. Chen L., Zuo M., Zhou Q., Wang Y. Oncolytic virotherapy in cancer treatment: challenges and optimization prospects // Front Immunol. – 2023. – Vol. 14. – P. 1308890. DOI: 10.3389/fimmu.2023.1308890

52. Kurokawa C., Iankov I.D., Anderson S.K., Aderca I., Leontovich A.A., Maurer M.J., Oberg A.L., Schroeder M.A., Giannini C., Greiner S.M., Becker M.A., Thompson E.A., Haluska P., Jentoft M.E., Parney I.F., Weroha S.J., Jen J., Sarkaria J.N., Galanis E. Constitutive interferon pathway activation in tumors as an efficacy determinant following oncolytic virotherapy // J Natl Cancer Inst. – 2018. – Vol. 110, No. 10. – P. 1123–1132. DOI: 10.1093/jnci/djy033

53. Ebrahimi S., Ghorbani E., Khazaei M., Avan A., Ryzhikov M., Azadmanesh K., Hassanian SM. Interferon-mediated tumor resistance to oncolyc virotherapy // J Cell Biochem. –2017. – Vol. 118. – P. 1994–1999. DOI: 10.1002/jcb.25917

54. Lin D., Shen Y., Liang T.L. Oncolytic virotherapy: basic principles, recent advances and future directions // Signal Transduction and Targeted Therapy. – 2023. – Vol. 8, No. 1. – P. 156. DOI: 10.1038/s41392-023-01407-6

55. Meyers D.E., Wang A.A., Thirukkumaran C.M., Morris D.G. Current immunotherapeutic strategies to enhance oncolytic virotherapy // Front Oncol. – 2017. – Vol. 7. – P. 114. DOI: 10.3389/fonc.2017.00114

56. Rasa A., Alberts P. Oncolytic virus preclinical toxicology studies // J Appl Toxicol. – 2023. – Vol. 43, No. 5. – P. 620–648. DOI: 10.1002/jat.4408

57. Alberts P., Tilgase A., Rasa A., Bandere K., Venskus D. The advent of oncolytic virotherapy in oncology: The Rigvir® story. Eur J Pharmacol. 2018. – Vol. 837. – P. 117–226. DOI: 10.1016/j.ejphar.2018.08.042

58. Tilgase A., Patetko L., Blāķe I., Ramata-Stunda A., Borodušķis M., Alberts P. Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro // J Cancer. – 2018. – Vol. 9, No. 6. – P. 1033–1049. DOI: 10.7150/jca.23242

59. Tilgase A., Grīne L., Blāķe I., Borodušķis M., Rasa A., Alberts P. Effect of oncolytic ECHO-7 virus strain Rigvir on uveal melanoma cell lines // BMC research Notes. – 2020. – Vol. 13, No. 1. – P. 222–222. DOI: 10.1186/s13104-020-05068-4

60. Piwoni K., Jaeckel G., Rasa A., Alberts P. 4-Week repeated dose rat GLP toxicity study of oncolytic ECHO-7 virus Rigvir administered intramuscularly with a 4-week recovery period // Toxicol Rep. – 2021. – Vol. 8. – P. 230–238. DOI: 10.1016/j.toxrep.2021.01.009

61. Annels N.E., Mansfield D., Arif M., Ballesteros-Merino C., Simpson G.R., Denyer M., Sandhu S.S., Melcher A.A., Harrington K.J., Davies B., Au G., Grose M., Bagwan I., Fox B., Vile R., Mostafid H., Shafren D., Pandha H.S. Phase I trial of an ICAM-1-targeted immunotherapeutic-coxsackievirus A21 (CVA21) as an oncolytic agent against non-muscle-invasive bladder cancer // Clin Cancer Res. – 2019. – Vol. 25, No. 19. – P. 5818–5831. DOI: 10.1158/1078-04321.CCr-18-4022

62. Hamid О., Ismail R., Puzanov I. Intratumoral immunotherapy-update 2019 // The Oncologist. – 2020. – Vol. 25, No. 3. – P. e423-e438. DOI: 10.1634/theoncologist.2019-0438

63. Au G.G., Lindberg A.M., Barry R.D., Shafren D.R. Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21 // Int J Oncol. – 2005. – Vol. 26, No. 6. – P. 1471–1476. DOI: 10.3892/ijo.26.6.1471

64. Skelding K.A., Barry R.D., Shafren D.R. Systemic targeting of metastatic human breast tumor xenografts by Coxsackievirus A21. Breast Cancer Research and Treatment. – 2009. – Vol. 113, No. 1. – P. 21–30. DOI: 10.1007/s10549-008-9899-2

65. Bradley S., Jakes A.D., Harrington K., Pandha H., Melcher A., Errington-Mais F. Application of coxsackievirus A21 in oncology // Oncolytic Virotherapy. – 2014. – Vol. 3. – P. 47–55. DOI: 10.2147/OV.S56322

66. Dighe O.R., Korde P., Bisen Y.T., Iratwar S., Kesharwani A., Vardhan S., Singh A. Emerging recombinant oncolytic poliovirus therapies against malignant glioma: A Review // Cureus. – 2023. – Vol. 15, No. 1. – P. e34028. DOI: 10.7759/cureus.34028

67. Gromeier M., Nair S.K. Recombinant poliovirus for cancer immunotherapy // Annu Rev Med. – 2018. – Vol. 69. – P. 289–299. DOI: 10.1146/annurev-med-050715-104655

68. Georgescu MM., Balanant J., Macadam A., Otelea D., Combiescu M., Combiescu AA., Crainic R., Delpeyroux F. Evolution of the Sabin type I poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis // J Virol. – 1997. – Vol. 71, No. 10. – P. 7758–7768. DOI: 10.1128/JVI.71.10.7758-7768.1997

69. Gromeier M., Alexander L., Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants // Proc Natl Acad Sci USA. – 1996. – Vol. 93, No. 6. – P. 2370–2375. DOI: 10.1073/pnas.93.6.2370

70. Dobrikova E.Y., Goetz C., Walters R.W., Lawson S.K., Peggins J.O., Muszynski K., Ruppel S., Poole K., Giardina S.L., Vela E.M., Estep J.E., Gromeier M. Attenuation of neurovirulence, biodistribution, and shedding of poliovirus:rhinovirus chimera after intrathalamic inoculation in Macaca fascicularis // J Virol. – 2012. – Vol. 86, No. 5. – P. 2750–2759. DOI: 10.1128/JVI.06427-11

71. Chandramohan V., Bryant J.D., Piao H., Keir S.T., Lipp E.S., Lefaivre M., Perkinson K., Bigner D.D., Gromeier M., McLendon RE. Validation and immunohistochemistry assay for detection of CD155, the poliovirus receptor in malignant gliomas // Arch Path Lab Med. – 2017. – Vol. 141, No. 12. – P. 1697–1704. DOI: 10.5858/arpa.2016-0580-OA

72. Paolini R., Molfetta R. CD155 and Its Receptors as Targets for Cancer Therapy // Int J Mol Sci. – 2023. – Vol. 24, No. 16. – P. 12958. DOI: 10.3390/ijms241612958

73. Blake S.J., Stannard K., Liu J., Allen S., Yong M.C., Mittal D., Aguilera A.R., Miles J.J., Lutzky V.P., de Andrade L.F., Martinet L., Colonna M., Takeda K., Kühnel F., Gurlevik E., Bernhardt G., Teng M.W., Smyth M.J. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy // Cancer Discov. – 2016. – Vol. 6, No. 4. – P. 446–459. DOI: 10.1158/2159-8290.CD-15-0944

74. Dougall W.C., Kurtulus S., Smyth M.J., Anderson A.C. TIGIT and CD96: new checkpoint receptor targetsfor cancer immunotherapy // Immunol Rev. – 2017. – Vol. 276, No. 1. – P. 112–120. DOI: 10.1111/imr.12518

75. Brown M.C., Gromeier M. Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus // Curr Opin Viro. – 2015. – Vol. 13. – P. 81–85. DOI: 10.1016/j.coviro.2015.05.007

76. Holl E.K., Brown M.C., Boczkowski D., McNamara M.A., George D.J., Bigner D.D., Gromeier M., Nair S.K. Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models // Oncotarget. – 2016. – Vol. 7, No. 48. – P. 79828–79841. DOI: 10.18632/oncotarget.12975

77. Varela M.L., Comba A., Faisal S.M., Argento A., Franson A., Barissi M.N., Sachdev S., Castro M.G., Lowenstein P.R. Gene therapy for high grade glioma: The clinical experience // Expert Opin Biol Ther. – 2023. – Vol. 23, No. 2. – P. 145–161. DOI: 10.1080/14712598.2022.2157718

78. Čēma I., Kleina R., Doniņa S., Isajevs S., Zablocka T., Rasa A., Alberts P. Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir // Perm J. – 2022. – Vol. 26, No. 3. – P. 139–144. DOI: 10.7812/TPP/21.232

79. Wei D., Xu J., Liu X.Y., Chen Z.N., Bian H. Fighting cancer with viruses: oncolytic virus therapy in China // Hum Gene Ther. – 2018. – Vol. 29, No. 2. – P. 151–159. DOI: 10.1089/hum.2017.212

80. Raman S.S., Hecht J.R., Chan E. Talimogene laherparepvec: Review of its mechanism of action and clinical efficacy and safety // Immunotherapy. – 2019. – Vol. 11, No. 8. – P. 705–723. DOI: 10.2217/imt-2019-0033

81. Malvehy J., Samoylenko I., Schadendorf D., Gutzmer R., Grob J.J., Sacco J.J. Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-labelstudy in patients with stage IIIB-IVM1c melanoma // J Immunother Cancer. – 2021. – Vol. 9, No. 3. – P. e001621. DOI: 10.1136/jitc-2020-001621

82. Andtbacka R.H.I., Amatruda T., Nemunaitis J., Zager J.S., Walker J., Chesney J.A., Liu K., Hsu C.P., Pickett C.A., Mehnert J.M. Biodistribution, shedding, and transmissibility of the oncolytic virus talimogene laherparepvec in patients with melanoma // EBioMedicine. – 2019. – Vol. 47. – P. 89–97. DOI: 10.1016/j.ebiom.2019.07.066

83. Andtbacka R.H.I., Collichio F., Harrington K.J., Middleton M.R., Downey G., Ӧhrling K., Kaufman L. Final analyses of OPTiM: a randomized phase III trial of Talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III-IV melanoma // J Immunother Cancer. – 2019. – Vol. 7, No. 1. – P. 145. DOI: 10.1186/s40425-019-0623-z

84. Sugawara K., Iwai M., Ito H., Tanaka M., Seto Y., Todo T. Oncolytic herpes virus G47Δ works synergistically with CTLA-4 inhibition via dynamic intratumoral immune modulation // Mol Ther Oncolytics. – 2021. – Vol. 22. – P. 129–142. DOI: 10.1016/j.omto.2021.05.004

85. Todo T., Ino Y., Ohtsu H., Shibahara J., Tanaka M. A phase I/II study of triple-mutated oncolytic herpes virus G47Δ in patients with progressive glioblastoma // Nat Commun. – 2022. – Vol. 13, No. 1. – P. 4119. DOI: 10.1038/s41467-022-31262-y

86. Todo T., Ito H., Ino Y., Ohtsu H., Ota Y., Shibahara J., Tanaka M. Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial // Nat Med. – 2022. – Vol. 28, No. 8. – P. 1630–1639. DOI: 10.1038/s41591-022-01897-x

87. Tamadaho R.S.E., Hoerauf A., Layland L.E. Immunomodulatory effects of myeloid-derived suppressor cells in diseases: role in cancer and infections // Immunobiology. – 2018. – Vol. 223, No. 4–5. – P. 432–442. DOI: 10.1016/j.imbio.2017.07.001

88. Yamazaki N., Isei T., Kiyohara Y., Koga H., Kojima T., Takenouchi T., Yokota K., Namikawa K., Yi M., Keegan A., Fukushima S. A phase I study of the safety and efficacy of talimogene laherparepvec in Japaneses patients with advanced melanoma // Cancer Sci. – 2022. – Vol. 113, No. 8. – P. 2798–2806. DOI: 10.1111/cas.15450

89. Andtbacka R.H.I., Curti B., Daniels G.A., Hallmeyer S., Whitman E.D., Lutzky J., Spitler L.E., Zhou K., Bommareddy P.K., Grose M., Wang M., Wu C., Kaufman H.L. Clinical responses of oncolytic coxsackievirus A21(V937) in patients with unresectable melanoma // J Clin Oncol. – 2021. – Vol. 39, No. 34. – P. 3829–3838. DOI: 10.1200/JCO.20.03246

90. Beasley G.M., Nair S.K., Farrow N.E., Landa K., Selim M., Wiggs C.A., Jung S.H., Bigner D.D., True Kelly A., Gromeier M., Salama A.K. Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma // J immunother Cancer. – 2021. – Vol. 9, No. 4. – P. e002203. DOI: 10.1136/jitc-2020-002203

91. Fares J., Ahmed AU., Ulasov I.V., Sonabend A.M., Miska J., Lee-Chang C., Balyasnikova I.V., Chandler J.P., Portnow J., Tate M.C., Kumthekar P., Lukas R.V., Grimm S.A., Adams A.K., Hébert C.D., Strong T.V., Amidei C., Arrieta V.A., Zannikou M., Horbinski C., Zhang H., Burdett K.B., Curiel D.T., Sachdev S., Aboody K.S., Stupp R., Lesniak M.S. Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase I, dose-escalation trial // Lancet Oncol. – 2021. – Vol. 22, No. 8. – P. 1103–1114. DOI: 10.1016/S1470-2045(21)00245-X

92. Friedman G.K., Johnston J.M., Bag A.K., Bernstock J.D., Li R., Aban I., Kachurak K., Nan L., Kang K.D., Totsch S., Schlappi C., Martin AM., Pastakia D., McNall-Knapp R., Farouk Sait S., Khakoo Y., Karajannis M.A., Woodling K., Palmer J.D., Osorio D.S., Leonard J., Abdelbaki M.S., Madan-Swain A., Atkinson T.P., Whitley R.J., Fiveash J.B., Markert J.M., Gillespie G.Y. Oncolytic HSV-1 G207 immunovirotherapy for pediatric high-grade gliomas // N Engl J Med. – 2021. – Vol. 384, No. 17. – P. 1613–1622. DOI: 10.1056/NEJMoa2024947

93. Desjardins A., Gromeier M., Herndon J.E. 2nd, Beaubier N., Bolognesi D.P., Friedman A.H., Friedman H.S., McSherry F., Muscat A.M., Nair S., Peters K.B., Randazzo D., Sampson J.H., Vlahovic G., Harrison W.T., McLendon R.E., Ashley D., Bigner D.D. Recurrent glioblastoma treated with recombinant poliovirus // N Engl J Med. – 2018. – Vol. 379, No. 2. – P. 150–161. DOI: 10.1056/NEJMoa1716435

94. Lauer U.M., Beil J. Oncolytic viruses: challenges and considerations in an evolving clinical landscape // Future Oncology. – 2022. – Vol. 18, No. 24. – P. 2713–2732. DOI: 10.2217/fon-2022-0440

95. Lutzky J., Sullivan R., Cohen J.V., Ren Y., Li A., Haq R. Phase 1b study of intravenous coxsackievirus A21(V937) and ipilimumab for patients with metastatic uveal melanoma // J Cancer Res Clin Oncol. – 2023. – Vol. 149, No. 9. – P. 6059–6066. DOI: 10.1007/s00432-022-04510-3

96. Olivet M.M., Brown M.C., Reitman Z.J., Ashley D.M., Grant G.A., Yang Y., Markert J.M. Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults // Cancers. – 2023. – Vol. 15, No. 15. – P. 3901. DOI: 10.3390/cancers15153901