Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC109110.15690/vramn1091ONCOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ОНКОЛОГИИOncolytic Viruses As Immunotherapeutic Agents for the Treatment of Malignant TumorsОнколитические вирусы как иммунотерапевтические агенты в лечении злокачественных новообразованийhttps://orcid.org/0000-0002-7371-1183GlukhovAlexander I.ГлуховАлександр Иванович
Russian Federation

PhD, professor.

119991, 8-2 Trubetskaya str., Moscow.

SPIN-код: 3926-8485

Профессор, доктор биологических наук, заведующий кафедрой биологической химии Первого МГМУ имени И. М. Сеченова (Сеченовский Университет); ведущий научный сотрудник, профессор Биологического факультета МГУ им. М.В. Ломоносова.

119991, Москва, ул. Трубецкая, д. 8, стр. 2.

SPIN-код: 3926-8485

aiglukhov1958@gmail.comhttps://orcid.org/0000-0001-7341-1167SivokhinDmitry A.СивохинДмитрий Алексеевич
Russian Federation

SPIN-код: 8362-3570

Студент.

SPIN-код: 8362-3570

d100s001@gmail.comhttps://orcid.org/0000-0003-3884-9256SeryakDaria A.СерякДарья Александровна
Russian Federation

SPIN-код: 8395-4172

Студентка.

SPIN-код: 8395-4172

daria.seriak@gmail.comhttps://orcid.org/0000-0003-0336-3459RodionovaTatyana S.РодионоваТатьяна Сергеевна
Russian Federation

SPIN-код: 5948-8248

Студентка.

SPIN-код: 5948-8248

tata92176@gmail.comhttps://orcid.org/0000-0001-8093-8151KamyninaMargarita I.КамынинаМаргарита Игоревна
Russian Federation

SPIN-код: 9756-5856

Студентка.

SPIN-код: 9756-5856

margaret.kamynina@gmail.comI.M. Sechenov First Moscow State Medical UniversityПервый Московский государственный медицинский университет имени И. М. Сеченова (Сеченовский Университет)M.V. Lovonosov Moscow State UniversityМосковский Государственный Университет им. М.В. Ломоносова310520197421081172512201807052019Copyright ©; 2019, "Paediatrician" Publishers LLCCopyright ©; 2019, Издательство "Педиатръ"2019"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1091

Oncolytic viruses (OVs) are novel and rapidly developing class of therapeutic agents for combating cancer, which can effectively infect and destroy tumor cells, leaving healthy tissues intact. Many viruses have a natural antitumor activity which causes cytolysis of cancer cells due to direct pathogenic action. Along with non-immunogenic cell death, oncolytic viruses have been shown to be capable of inducing immunogenic cancer cell death (necrosis, pyroptosis, etc.) accompanied by the release of OV-lysed tumor-associated antigens (TAAs). Releasing DAMPs and TAAs, in its turn, leads to the activation of adaptive antitumor immunity. In order to further enhance the antitumor immunity, OVs have been armed with immunostimulatory transgenes such as granulocyte-macrophage colony-stimulating factor (GM-CSF), type I interferons, interleukins (IL-2, 12, 15), costimulatory ligands (CD40, CD80), tumor antigens («prime-boost» vaccination), which further enhances the safety and effectiveness of oncolytic virotherapy. Preliminary results of randomized clinical trials of different approaches of oncolytic virotherapies in combination with immunotherapy confirm their high efficacy. However, there are some drawbacks, which necessitates their further study.

Онколитические вирусы представляют собой стремительно развивающийся класс терапевтических агентов для борьбы со злокачественными новообразованиями, которые позволяют эффективно инфицировать и разрушать опухолевые клетки, оставляя интактными здоровые ткани. Многие вирусы обладают естественной противоопухолевой активностью, вызывая цитолиз раковых клеток за счет прямого патогенного действия. Однако наряду с неиммуногенной клеточной гибелью онколитические вирусы способны индуцировать иммуногенные формы клеточной смерти (иммуногенный апоптоз, пироптоз и др.), сопровождающиеся высвобождением из опухолевых клеток DAMPs (молекулярных паттернов, ассоциированных с повреждением) и ТААs (опухольассоцированных антигенов), что приводит к активации адаптивного противоопухолевого иммунного ответа. Естественная активация иммунитета в результате вирусной инфекции оказывается, однако, недостаточно эффективной для уничтожения опухоли, что может быть решено путем создания генно-модифицированных штаммов различных вирусов, в которые встраиваются иммуностимулирующие трансгены: гранулоцитарно-макрофагальный колониестимулирующий фактор (GM-CSF), интерлейкины (IL2, 15, 12), ТАА или костимулирующие лиганды (CD), а также используется подход «prime-boost», что дополнительно повышает безопасность и эффективность онколитической виротерапии. Предварительные результаты рандомизированных клинических испытаний рекомбинантных онколитических вирусов с повышенной иммуногенностью подтверждают их эффективность, однако для создания полноценных препаратов для онкотерапии на основе онколитических вирусов требуется дальнейшая оптимизация этих подходов.

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