ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2024-4-158-168ssmu-5883Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESКлинические исследования онколитических вирусовClinical trials on oncolytic viruseshttps://orcid.org/0000-0003-3011-6904ГоловиновИ. В.GolovinovI. V.

Головинов Игорь Викторович – мл. науч. сотрудник, испытательный лабораторный центр, 

344037, г. Ростов-на-Дону, ул. 14-я Линия, 63

63, 14 Liniya Str., Rostov-on-Don, 344037

ivgolovinov@yandex.ruhttps://orcid.org/0000-0003-0676-0871ГончароваА. С.GoncharovaA. S.

Гончарова Анна Сергеевна – канд. биол. наук, зав. испытательным лабораторным центром, 

344037, г. Ростов-на-Дону, ул. 14-я Линия, 63

63, 14 Liniya Str., Rostov-on-Don, 344037

fateyeva_a_s@list.ruhttps://orcid.org/0009-0006-1125-2897ШульгаА. А.ShulgaA. A.

Шульга Анна Александровна – мл. науч. сотрудник, испытательный лабораторный центр, 

344037, г. Ростов-на-Дону, ул. 14-я Линия, 63

63, 14 Liniya Str., Rostov-on-Don, 344037

slip.anka96@mail.ruhttps://orcid.org/0000-0003-3289-8436ВласовС. Н.VlasovS. N.

Власов Сергей Николаевич – студент 4-го курса, лечебно-профилактический факультет,

344022, г. Ростов-на-Дону, пер. Нахичеванский, 29

29, Nakhichevanskiy Av., Rostov-on-Don, 344022

ser.vl4s0v02@yandex.ruhttps://orcid.org/0000-0002-2565-1518ДимитриадиС. Н.DimitriadiS. N.

Димитриади Сергей Николаевич – д-р мед. наук, ст. науч. сотрудник, отделение онкоурологии, 

344037, г. Ростов-на-Дону, ул. 14-я Линия, 63 

63, 14 Liniya Str., Rostov-on-Don, 344037

Dimitriadi.pro@gmail.comНациональный медицинский исследовательский центр (НМИЦ) онкологииРоссияNational Medical Research Center for OncologyRussian FederationРостовский государственный медицинский университет (РостГМУ)РоссияRostov State Medical UniversityRussian Federation202427012025234158168Copyright © Головинов И.В., Гончарова А.С., Шульга А.А., Власов С.Н., Димитриади С.Н., 20252025Головинов И.В., Гончарова А.С., Шульга А.А., Власов С.Н., Димитриади С.Н.Golovinov I.V., Goncharova A.S., Shulga A.A., Vlasov S.N., Dimitriadi S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5883

Онколитические вирусы (ОВ) – это новый класс таргетных противоопухолевых препаратов, обладающих уникальными механизмами действия. Эволюция в области виротерапии прошла от использования штаммов, пассированных in vitro (первое поколение), к генно-инженерным вирусам с повышенной селективностью (второе поколение) и, в конечном итоге, к рекомбинантным ОВ, экспрессирующим трансгены (третье поколение).

Цель обзора заключалась в проведении анализа и обобщении данных о текущей ситуации в клинических исследованиях ОВ.

Поиск в PubMed за период с 1997 по 2024 г. выявил 182 статьи, из которых 154 предоставили данные о 4 850 пациентах. Согласно публикациям, аденовирус (n = 44) является наиболее распространенным ОВ в клинических исследованиях, причем более двух третей (n = 108) использовали модифицированные или рекомбинантные вирусные основы с наиболее частым трансгеном в виде гранулоцитарно-макрофагального колониестимулирующего фактора (GM-CSF; n = 40). Среди опухолей в большинстве случаев исследовались меланома (n = 1 997) и рак желудочно-кишечного тракта (ЖКТ; n = 916) с использованием преимущественно монотерапии ОВ через внутриопухолевое (n = 3 003) или внутривенное (n = 1 318) введение. Часто встречающаяся комбинация включала химиотерапию (n = 54).

Нежелательными явлениями, связанными с лечением ОВ, были конституциональные симптомы низкой степени тяжести и местные реакции в месте инъекции. Часто проводили измерения выделения вируса, однако во многих исследованиях ограничивались анализом крови и опухолевой ткани, применяя только полимеразную цепную реакцию. Несмотря на то, что в большинстве работ сообщали о титрах противовирусных антител (n = 101), лишь в некоторых были отмечены вирусспецифические Т-клеточные ответы (n = 23). Объективные ответы (ORR, objective response rate) были зафиксированы у 458 (9,4%) пациентов, а контроль заболевания достигался у 1 141 (23,5%) больного, хотя стандартные критерии отчетности использовались лишь в 60,4% случаев.

Эти данные дают представление о текущем состоянии клинических исследований ОВ и выявляют потенциальные области, требующие дальнейшего изучения для более четкого определения роли ОВ в лечении рака.

Oncolytic viruses (OVs) are a new class of targeted anticancer drugs with unique mechanisms of action. Oncolytic virotherapy has evolved from the use of in vitro-passaged strains (first generation) to genetically engineered viruses with increased selectivity (second generation) and, ultimately, to recombinant OVs expressing a transgene (third generation).

The aim of the review was to analyze and summarize data on the current state of clinical research on OVs.

A PubMed search identified 182 articles from 1997 to 2024 with 154 studies reporting data on 4,850 patients. We found that adenovirus (n = 44) is the most common OV in clinical trials with more than two-thirds (n = 108) using modified or recombinant viral backbones, and granulocyte-macrophage colony-stimulating factor (GM-CSF; n = 40) was the most common transgene. The most common tumors targeted were melanoma (n = 1,997) and gastrointestinal (GI; n = 916) cancers with the most common monotherapy received by intratumoral (n = 3,003) or intravenous (n = 1,318) delivery routes. The most common combination included chemotherapy (n = 54).

Treatment-related adverse events included low-grade constitutional symptoms and local injection site reactions. Measurements of virus shedding were frequently performed, but many studies were limited to blood and tumor tissue analysis, using only polymerase chain reaction (PCR). Although most studies reported antiviral antibody titers (n = 101), only a few reported virus-specific T-cell responses (n = 23). Objective responses were recorded in 458 (9.4%) patients and disease control was achieved in 1,141 (23.5%) patients, although standard reporting criteria were used in only 60.4% of cases.

These data provide an insight into the current state of clinical research on OVs and highlight potential areas requiring further investigation to better define the role of OVs in cancer treatment.

онколитический вирусиммунотерапиявиротерапияклинические исследованияклинические испытанияoncolytic virusimmunotherapyvirotherapyclinical researchclinical trialsReferencesDebela D.T., Muzazu S.G., Heraro K.D., Ndalama M.T., Mesele B.W., Haile D.C. et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9:1–10. DOI: 10.1177/20503121211034366.Debela D.T., Muzazu S.G., Heraro K.D., Ndalama M.T., Mesele B.W., Haile D.C. et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Med. 2021;9:1–10. DOI: 10.1177/20503121211034366.Кит О.И., Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н. и др. Иммунотерапия эпителиальных опухолей вилочковой железы. Южно-Российский онкологический журнал. 2023;4(3):56–67. DOI: 10.37748/2686-9039-2023-4-3-7.Кит О.И., Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н. и др. Иммунотерапия эпителиальных опухолей вилочковой железы. Южно-Российский онкологический журнал. 2023;4(3):56–67. DOI: 10.37748/2686-9039-2023-4-3-7.Santos Apolonio J., Lima de Souza Gonçalves V., Cordeiro Santos M.L., Silva Luz M., Silva Souza J.V., Rocha Pinheiro S.L. et al. Oncolytic virus therapy in cancer: A current review. World J. Virol. 2021;10(5):229–255. DOI: 10.5501/wjv.v10. i5.229.Santos Apolonio J., Lima de Souza Gonçalves V., Cordeiro Santos M.L., Silva Luz M., Silva Souza J.V., Rocha Pinheiro S.L. et al. Oncolytic virus therapy in cancer: A current review. World J. Virol. 2021;10(5):229–255. DOI: 10.5501/wjv.v10. i5.229.Hemminki O., Dos Santos J.M., Hemminki A. Oncolytic viruses for cancer immunotherapy. J. Hematol. Oncol. 2020;13(1):84. DOI: 10.1186/s13045-020-00922-1.Hemminki O., Dos Santos J.M., Hemminki A. Oncolytic viruses for cancer immunotherapy. J. Hematol. Oncol. 2020;13(1):84. DOI: 10.1186/s13045-020-00922-1.Heidbuechel J.P.W., Engeland C.E. Oncolytic viruses encoding bispecific T cell engagers: a blueprint for emerging immunovirotherapies. J. Hematol. Oncol. 2021;14(1):63. DOI: 10.1186/s13045-021-01075-5.Heidbuechel J.P.W., Engeland C.E. Oncolytic viruses encoding bispecific T cell engagers: a blueprint for emerging immunovirotherapies. J. Hematol. Oncol. 2021;14(1):63. DOI: 10.1186/s13045-021-01075-5.Cristi F., Gutiérrez T., Hitt M.M., Shmulevitz M. Genetic modifications that expand oncolytic virus potency. Front. Mol. Biosci. 2022;9:831091. DOI: 10.3389/fmolb.2022.831091.Cristi F., Gutiérrez T., Hitt M.M., Shmulevitz M. Genetic modifications that expand oncolytic virus potency. Front. Mol. Biosci. 2022;9:831091. DOI: 10.3389/fmolb.2022.831091.Silva Lima B., Videira M.A. Toxicology and biodistribution: the clinical value of animal biodistribution studies. Mol. Ther. Methods Clin. Dev. 2018;8:183–197. DOI: 10.1016/j.omtm.2018.01.003.Silva Lima B., Videira M.A. Toxicology and biodistribution: the clinical value of animal biodistribution studies. Mol. Ther. Methods Clin. Dev. 2018;8:183–197. DOI: 10.1016/j.omtm.2018.01.003.Yamaguchi T., Uchida E. Oncolytic virus: regulatory aspects from quality control to clinical studies. Curr. Cancer Drug Targets. 2018;18(2):202–208. DOI: 10.2174/1568009617666170222142650.Yamaguchi T., Uchida E. Oncolytic virus: regulatory aspects from quality control to clinical studies. Curr. Cancer Drug Targets. 2018;18(2):202–208. DOI: 10.2174/1568009617666170222142650.Russell S.J., Peng K.W. Oncolytic virotherapy: a contest between apples and oranges. Mol. Ther. 2017;25(5):1107–1116. DOI: 10.1016/j.ymthe.2017.03.026.Russell S.J., Peng K.W. Oncolytic virotherapy: a contest between apples and oranges. Mol. Ther. 2017;25(5):1107–1116. DOI: 10.1016/j.ymthe.2017.03.026.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):4192–4206.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):4192–4206.Кит О.И., Игнатов С.Н., Златник Е.Ю., Солдаткина Н.В., Росторгуев Э.Е., Сагакянц А.Б., Бондаренко Е.С. и др. Онколитическая виротерапия в лечении глиобластомы: достижения и проблемы клинических исследований (обзор литературы). Сибирский онкологический журнал. 2020;19(6):133–140. DOI: 10.21294/1814-4861-2020-19-6-133-140.Кит О.И., Игнатов С.Н., Златник Е.Ю., Солдаткина Н.В., Росторгуев Э.Е., Сагакянц А.Б., Бондаренко Е.С. и др. Онколитическая виротерапия в лечении глиобластомы: достижения и проблемы клинических исследований (обзор литературы). Сибирский онкологический журнал. 2020;19(6):133–140. DOI: 10.21294/1814-4861-2020-19-6-133-140.Abou-Alfa G.K., Galle P.R., Chao Y., Erinjeri J., Heo J., Borad M.J. et al. PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Liver Cancer. 2023;1–17. DOI: 10.1159/000533650.Abou-Alfa G.K., Galle P.R., Chao Y., Erinjeri J., Heo J., Borad M.J. et al. PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Liver Cancer. 2023;1–17. DOI: 10.1159/000533650.Rahman M.M., McFadden G. Oncolytic viruses: newest frontier for cancer immunotherapy. Cancers (Basel). 2021;13(21):5452. DOI: 10.3390/cancers13215452.Rahman M.M., McFadden G. Oncolytic viruses: newest frontier for cancer immunotherapy. Cancers (Basel). 2021;13(21):5452. DOI: 10.3390/cancers13215452.Aiuti A., Cossu G., de Felipe P., Galli M.C., Narayanan G., Renner M. et al. The committee for advanced therapies’ of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis. Hum. Gene Ther. Clin. Dev. 2013;24(2):47–54. DOI: 10.1089/humc.2013.119.Aiuti A., Cossu G., de Felipe P., Galli M.C., Narayanan G., Renner M. et al. The committee for advanced therapies’ of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis. Hum. Gene Ther. Clin. Dev. 2013;24(2):47–54. DOI: 10.1089/humc.2013.119.Kaufman H.L., Kohlhapp F.J., Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 2015;14(9):642–662. DOI: 10.1038/nrd4663.Kaufman H.L., Kohlhapp F.J., Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 2015;14(9):642–662. DOI: 10.1038/nrd4663.Appaiahgari M.B., Vrati S. Adenoviruses as gene/vaccine delivery vectors: promises and pitfalls. Expert Opin. Biol. Ther. 2015;15(3):337–351. DOI: 10.1517/14712598.2015.993374.Appaiahgari M.B., Vrati S. Adenoviruses as gene/vaccine delivery vectors: promises and pitfalls. Expert Opin. Biol. Ther. 2015;15(3):337–351. DOI: 10.1517/14712598.2015.993374.Sena-Esteves M., Gao G. Introducing genes into mammalian cells: viral vectors. Cold Spring Harb. Protoc. 2020;2020(8):095513. DOI: 10.1101/pdb.top095513.Sena-Esteves M., Gao G. Introducing genes into mammalian cells: viral vectors. Cold Spring Harb. Protoc. 2020;2020(8):095513. DOI: 10.1101/pdb.top095513.Kumar A., Taghi Khani A., Sanchez Ortiz A., Swaminathan S. GM-CSF: a double-edged sword in cancer immunotherapy. Front. Immunol. 2022;13:901277. DOI: 10.3389/fimmu.2022.901277.Kumar A., Taghi Khani A., Sanchez Ortiz A., Swaminathan S. GM-CSF: a double-edged sword in cancer immunotherapy. Front. Immunol. 2022;13:901277. DOI: 10.3389/fimmu.2022.901277.Zhao Y., Liu Z., Li L., Wu J., Zhang H., Zhang H. et al. Oncolytic adenovirus: prospects for cancer immunotherapy. Front. Microbiol. 2021;12:707290. DOI: 10.3389/fmicb.2021.707290.Zhao Y., Liu Z., Li L., Wu J., Zhang H., Zhang H. et al. Oncolytic adenovirus: prospects for cancer immunotherapy. Front. Microbiol. 2021;12:707290. DOI: 10.3389/fmicb.2021.707290.Woo S.R., Fuertes M.B., Corrales L., Spranger S., Furdyna M.J., Leung M.Y. et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41(5):830–842. DOI: 10.1016/j.immuni.2014.10.017.Woo S.R., Fuertes M.B., Corrales L., Spranger S., Furdyna M.J., Leung M.Y. et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41(5):830–842. DOI: 10.1016/j.immuni.2014.10.017.Iurescia S., Fioretti D., Rinaldi M. Targeting cytosolic nucleic acid-sensing pathways for cancer immunotherapies. Front. Immunol. 2018;9:711. DOI: 10.3389/fimmu.2018.00711.Iurescia S., Fioretti D., Rinaldi M. Targeting cytosolic nucleic acid-sensing pathways for cancer immunotherapies. Front. Immunol. 2018;9:711. DOI: 10.3389/fimmu.2018.00711.Andtbacka R.H.I., Collichio F., Harrington K.J., Middleton M.R., Downey G., Ӧhrling K. et al. 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;7(1):145. DOI: 10.1186/s40425-019-0623-z.Andtbacka R.H.I., Collichio F., Harrington K.J., Middleton M.R., Downey G., Ӧhrling K. et al. 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;7(1):145. DOI: 10.1186/s40425-019-0623-z.Zhang B., Cheng P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol. Cancer. 2020;19(1):158. DOI: 10.1186/s12943-020-01275-6.Zhang B., Cheng P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol. Cancer. 2020;19(1):158. DOI: 10.1186/s12943-020-01275-6.Soliman H., Hogue D., Han H., Mooney B., Costa R., Lee M.C. et al. Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial. Nat. Med. 2023;29(2):450–457. DOI: 10.1038/s41591-023-02210-0.Soliman H., Hogue D., Han H., Mooney B., Costa R., Lee M.C. et al. Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial. Nat. Med. 2023;29(2):450–457. DOI: 10.1038/s41591-023-02210-0.Ren Y., Miao J.M., Wang Y.Y., Fan Z., Kong X.B., Yang L. et al. Oncolytic viruses combined with immune checkpoint therapy for colorectal cancer is a promising treatment option. Front. Immunol. 2022;13:961796. DOI: 10.3389/fimmu.2022.961796.Ren Y., Miao J.M., Wang Y.Y., Fan Z., Kong X.B., Yang L. et al. Oncolytic viruses combined with immune checkpoint therapy for colorectal cancer is a promising treatment option. Front. Immunol. 2022;13:961796. DOI: 10.3389/fimmu.2022.961796.Monge C., Xie C., Myojin Y., Coffman K., Hrones D.M., Wang S. et al. Phase I/II study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer. J. Immunother. Cancer. 2023;11(2):e005640. DOI: 10.1136/jitc-2022-005640.Monge C., Xie C., Myojin Y., Coffman K., Hrones D.M., Wang S. et al. Phase I/II study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer. J. Immunother. Cancer. 2023;11(2):e005640. DOI: 10.1136/jitc-2022-005640.Liu X., Zhang J., Feng K., Wang S., Chen L., Niu S. et al. Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis. Front. Pharmacol. 2022;13:1023533. DOI: 10.3389/fphar.2022.1023533.Liu X., Zhang J., Feng K., Wang S., Chen L., Niu S. et al. Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis. Front. Pharmacol. 2022;13:1023533. DOI: 10.3389/fphar.2022.1023533.Zhang B., Cheng P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol. Cancer. 2020;19(1):158. DOI: 10.1186/s12943-020-01275-6.Zhang B., Cheng P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol. Cancer. 2020;19(1):158. DOI: 10.1186/s12943-020-01275-6.Passaro C., Alayo Q., De Laura I., McNulty J., Grauwet K., Ito H. et al. Arming an oncolytic herpes simplex virus type 1 with a single-chain fragment variable antibody against PD-1 for experimental glioblastoma therapy. Clin. Cancer Res. 2019;25(1):290–299. DOI: 10.1158/1078-0432.CCR-18-2311.Passaro C., Alayo Q., De Laura I., McNulty J., Grauwet K., Ito H. et al. Arming an oncolytic herpes simplex virus type 1 with a single-chain fragment variable antibody against PD-1 for experimental glioblastoma therapy. Clin. Cancer Res. 2019;25(1):290–299. DOI: 10.1158/1078-0432.CCR-18-2311.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. DOI: 10.3389/fmicb.2023.1188526.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. DOI: 10.3389/fmicb.2023.1188526.Ji W., Li L., Zhou S., Qiu L., Qian Z., Zhang H. et al. Combination immunotherapy of oncolytic virus nanovesicles and PD-1 blockade effectively enhances therapeutic effects and boosts antitumour immune response. J. Drug Target. 2020;28(9):982– 990. DOI: 10.1080/1061186X.2020.1766473.Ji W., Li L., Zhou S., Qiu L., Qian Z., Zhang H. et al. Combination immunotherapy of oncolytic virus nanovesicles and PD-1 blockade effectively enhances therapeutic effects and boosts antitumour immune response. J. Drug Target. 2020;28(9):982– 990. DOI: 10.1080/1061186X.2020.1766473.Chen L., Ma Z., Xu C., Xie Y., Ouyang D., Song S., Zhao X. et al. Progress in oncolytic viruses modified with nanomaterials for intravenous application. Cancer Biol. Med. 2023;20(11):830– 855. DOI: 10.20892/j.issn.2095-3941.2023.0275.Chen L., Ma Z., Xu C., Xie Y., Ouyang D., Song S., Zhao X. et al. Progress in oncolytic viruses modified with nanomaterials for intravenous application. Cancer Biol. Med. 2023;20(11):830– 855. DOI: 10.20892/j.issn.2095-3941.2023.0275.Ban W., Guan J., Huang H., He Z., Sun M., Liu F. et al. Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy. Nano Res. 2022;15(5):4137–4153. DOI: 10.1007/s12274-021-4031-6.Ban W., Guan J., Huang H., He Z., Sun M., Liu F. et al. Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy. Nano Res. 2022;15(5):4137–4153. DOI: 10.1007/s12274-021-4031-6.Fares J., Ahmed A.U., Ulasov I.V., Sonabend A.M., Miska J., Lee-Chang C., Balyasnikova I.V. et al. Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malig nant glioma: a first-in-human, phase 1, dose-escalation trial. Lancet Oncol. 2021;22(8):1103–1114. DOI: 10.1016/S1470-2045(21)00245-X.Fares J., Ahmed A.U., Ulasov I.V., Sonabend A.M., Miska J., Lee-Chang C., Balyasnikova I.V. et al. Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malig nant glioma: a first-in-human, phase 1, dose-escalation trial. Lancet Oncol. 2021;22(8):1103–1114. DOI: 10.1016/S1470-2045(21)00245-X.Fujita K., Kato T., Hatano K., Kawashima A., Ujike T., Uemura M. et al. Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer. Cancer Sci. 2020;111(5):1692–1698. DOI: 10.1111/cas.14366.Fujita K., Kato T., Hatano K., Kawashima A., Ujike T., Uemura M. et al. Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer. Cancer Sci. 2020;111(5):1692–1698. DOI: 10.1111/cas.14366.Silk A.W., O’Day S.J., Kaufman H.L., Bryan J., Norrell J.T., Imbergamo C. et al. A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study. Cancer Immunol. Immunother. 2023;72(6):1405–1415. DOI: 10.1007/s00262-022-03314-1.Silk A.W., O’Day S.J., Kaufman H.L., Bryan J., Norrell J.T., Imbergamo C. et al. A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study. Cancer Immunol. Immunother. 2023;72(6):1405–1415. DOI: 10.1007/s00262-022-03314-1.Nawrocki S.T., Olea J., Villa Celi C., Dadrastoussi H., Wu K., Tsao-Wei D. et al. Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial. Clin. Cancer Res. 2023;29(24):5087–5103. DOI: 10.1158/1078-0432.CCR-23-0229.Nawrocki S.T., Olea J., Villa Celi C., Dadrastoussi H., Wu K., Tsao-Wei D. et al. Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial. Clin. Cancer Res. 2023;29(24):5087–5103. DOI: 10.1158/1078-0432.CCR-23-0229.Hill C., Carlisle R. Achieving systemic delivery of oncolytic viruses. Expert Opin. Drug Deliv. 2019;16(6):607–620. DOI: 10.1080/17425247.2019.1617269.Hill C., Carlisle R. Achieving systemic delivery of oncolytic viruses. Expert Opin. Drug Deliv. 2019;16(6):607–620. DOI: 10.1080/17425247.2019.1617269.Naumenko V., Van S., Dastidar H., Kim D.S., Kim S.J., Zeng Z. Visualizing oncolytic virus-host interactions in live mice using intravital microscopy. Mol. Ther. Oncolytics. 2018;10:14–27. DOI: 10.1016/j.omto.2018.06.001.Naumenko V., Van S., Dastidar H., Kim D.S., Kim S.J., Zeng Z. Visualizing oncolytic virus-host interactions in live mice using intravital microscopy. Mol. Ther. Oncolytics. 2018;10:14–27. DOI: 10.1016/j.omto.2018.06.001.Bulcha J.T., Wang Y., Ma H., Tai P.W.L., Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target Ther. 2021;6(1):53. DOI: 10.1038/s41392-021-00487-6.Bulcha J.T., Wang Y., Ma H., Tai P.W.L., Gao G. Viral vector platforms within the gene therapy landscape. Signal Transduct. Target Ther. 2021;6(1):53. DOI: 10.1038/s41392-021-00487-6.Bubela T., Boch R., Viswanathan S. Recommendations for regulating the environmental risk of shedding for gene therapy and oncolytic viruses in Canada. Front. Med. (Lausanne). 2019;6:58. DOI: 10.3389/fmed.2019.00058.Bubela T., Boch R., Viswanathan S. Recommendations for regulating the environmental risk of shedding for gene therapy and oncolytic viruses in Canada. Front. Med. (Lausanne). 2019;6:58. DOI: 10.3389/fmed.2019.00058.Onnockx S., Baldo A., Pauwels K. Oncolytic viruses: an inventory of shedding data from clinical trials and elements for the environmental risk assessment. Vaccines (Basel). 2023;11(9):1448. DOI: 10.3390/vaccines11091448.Onnockx S., Baldo A., Pauwels K. Oncolytic viruses: an inventory of shedding data from clinical trials and elements for the environmental risk assessment. Vaccines (Basel). 2023;11(9):1448. DOI: 10.3390/vaccines11091448.Berkeley R.A., Steele L.P., Mulder A.A., van den Wollenberg D.J.M., Kottke T.J., Thompson J. et al. Antibody-neutralized reovirus is effective in oncolytic virotherapy. Cancer Immunol. Res. 2018;6(10):1161–1173. DOI: 10.1158/2326-6066.CIR-18-0309.Berkeley R.A., Steele L.P., Mulder A.A., van den Wollenberg D.J.M., Kottke T.J., Thompson J. et al. Antibody-neutralized reovirus is effective in oncolytic virotherapy. Cancer Immunol. Res. 2018;6(10):1161–1173. DOI: 10.1158/2326-6066.CIR-18-0309.Alberts P., Tilgase A., Rasa A., Bandere K., Venskus D. The advent of oncolytic virotherapy in oncology: The Rigvir® story. Eur. J. Pharmacol. 2018;837:117–126. DOI: 10.1016/j.ejphar.2018.08.042.Alberts P., Tilgase A., Rasa A., Bandere K., Venskus D. The advent of oncolytic virotherapy in oncology: The Rigvir® story. Eur. J. Pharmacol. 2018;837:117–126. DOI: 10.1016/j.ejphar.2018.08.042.Xia Z.J., Chang J.H., Zhang L., Jiang W.Q., Guan Z.Z., Liu J.W. et al. Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus. Ai Zheng. 2004;23(12):1666–1670.Xia Z.J., Chang J.H., Zhang L., Jiang W.Q., Guan Z.Z., Liu J.W. et al. Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus. Ai Zheng. 2004;23(12):1666–1670.Andtbacka R.H., Kaufman H.L., Collichio F., Amatruda T., Senzer N., Chesney J. et al. talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 2015;33(25):2780–2788. DOI: 10.1200/JCO.2014.58.3377.Andtbacka R.H., Kaufman H.L., Collichio F., Amatruda T., Senzer N., Chesney J. et al. talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 2015;33(25):2780–2788. DOI: 10.1200/JCO.2014.58.3377.Frampton J.E. Teserpaturev/G47Δ: first approval. BioDrugs. 2022;36(5):667–672. DOI: 10.1007/s40259-022-00553-7.Frampton J.E. Teserpaturev/G47Δ: first approval. BioDrugs. 2022;36(5):667–672. DOI: 10.1007/s40259-022-00553-7.Forbes N.S., Coffin R.S., Deng L., Evgin L., Fiering S., Giacalone M. et al. White paper on microbial anti-cancer therapy and prevention. J. Immunother. Cancer. 2018;6(1):78. DOI: 10.1186/s40425-018-0381-3.Forbes N.S., Coffin R.S., Deng L., Evgin L., Fiering S., Giacalone M. et al. White paper on microbial anti-cancer therapy and prevention. J. Immunother. Cancer. 2018;6(1):78. DOI: 10.1186/s40425-018-0381-3.Lawler S.E., Speranza M.C., Cho C.F., Chiocca E.A. Oncolytic viruses in cancer treatment: a review. JAMA Oncol. 2017;3(6):841–849. DOI: 10.1001/jamaoncol.2016.2064.Lawler S.E., Speranza M.C., Cho C.F., Chiocca E.A. Oncolytic viruses in cancer treatment: a review. JAMA Oncol. 2017;3(6):841–849. DOI: 10.1001/jamaoncol.2016.2064.Omole R.K., Oluwatola O., Akere M.T., Eniafe J., Agboluaje E.O., Daramola O.B. et al. Comprehensive assessment on the applications of oncolytic viruses for cancer immunotherapy. Front. Pharmacol. 2022;13:1082797. DOI: 10.3389/fphar.2022.1082797.Omole R.K., Oluwatola O., Akere M.T., Eniafe J., Agboluaje E.O., Daramola O.B. et al. Comprehensive assessment on the applications of oncolytic viruses for cancer immunotherapy. Front. Pharmacol. 2022;13:1082797. DOI: 10.3389/fphar.2022.1082797.

The authors declare that there are no conflicts of interest present.