Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology1883010.36233/0372-9311-638NXCMRVSCIENCE AND PRACTICEНАУКА И ПРАКТИКАResearch ArticleStreptococcal effective molecules as promising antiсancer agents: pros and consЭффекторные молекулы стрептококков как перспективные противоопухолевые средства: плюсы и минусыhttps://orcid.org/0000-0003-2312-5589SuvorovAlexander N.СуворовАлександр Николаевич
Russian Federation

Dr. Sci. (Med.), Professor, Corresponding Member of the RАS, Head, A.A. Totolyan microbiology department, Head, Department of fundamental problems of medicine and medical technologies

доктор мед. наук, профессор, член-корреспондент РАН, зав. отд. микробиологии им. акад. РАН А.А. Тотоляна, зав. каф. фундаментальных проблем медицины и медицинских технологий

alexander_suvorov1@hotmail.comhttps://orcid.org/0000-0001-7878-6339TsapievaAnna N.ЦапиеваАнна Николаевна
Russian Federation

Cand. Sci. (Biol.), senior researcher, Laboratory of biomedical microecology, A.A. Totolyan microbiology department

кандидат биол. наук, старший научный сотрудник лаб. биомедицинской микроэкологии отд. микробиологии им. акад. РАН А.А. Тотоляна

anna.tsapieva@gmail.comhttps://orcid.org/0000-0003-2464-7370ChernovAlexander N.ЧерновАлександр Николаевич
Russian Federation

Cand. Sci. (Biol.), senior researcher, Department of general pathology and pathological physiology, A.A. Totolyan microbiology department, Assistant, Department of Biological Chemistry

кандидат биол. наук, старший научный сотрудник отд. общей патологии и патологической физиологии и микробиологии им. акад. РАН А.А. Тотоляна, ассистент каф. биологической химии

al.chernov@mail.ruInstitute of Experimental MedicineИнститут экспериментальной медициныSaint Petersburg State UniversityСанкт-Петербургский государственный университетSaint Petersburg State Pediatric Medical UniversityСанкт-Петербургский государственный педиатрический медицинский университет1205202510222232381005202510052025Copyright ©; 2025, Suvorov A.N., Tsapieva A.N., Chernov A.N.Copyright ©; 2025, Суворов А.Н., Цапиева А.Н., Чернов А.Н.2025Suvorov A.N., Tsapieva A.N., Chernov A.N.Суворов А.Н., Цапиева А.Н., Чернов А.Н.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/18830

Oncological diseases remain the main cause of death and disability of the population worldwide. The most malignant types of cancer include of pancreas, liver and brain tumors. Modern methods of therapy (including chemoradiation, targeted and immune therapy) do not allow achieving the desired effectiveness in this group of patients. In this regard, new approaches to the treatment of oncological diseases are needed.

The aim of this review was to discuss the mechanisms of anticancer action of Strepococcus pyogenes and other streptococcal species, as well as to consider their cancer-stimulating effects and their limitations.

The review considers the current state of the problem of using bacterial oncotherapy involving streptococci A group (in particular, S. pyogenes). The involvement of S. pyogenes pathogenicity factors is discussed: M-protein, exotoxins: streptolysins S, O, superantigens, arginine deiminase, etc., as well as molecular mechanisms mediated by the host immune system cells. The authors' own data show that S. pyogenes exhibits selective M-protein-mediated cytolytic activity against C6 glioma and pancreatic adenocarcinoma (Panc) tumor cells and no activity against normal fibroblasts. The data on preclinical and clinical application of the streptococcal-based medicine OK-432 for the therapy of oncological diseases are briefly summarized. Tumor-associated properties of streptococci (induction of cytokine storm, proliferation, migration and angiogenesis of vascular epithelial cells, formation of neutrophil extracellular traps in the tumor microenvironment) caused by their interaction with immune cells of the tumor-bearing organism are also discussed.

Conclusion. The research data presented in this review convincingly demonstrate that S. pyogenes, with the participation of pathogenicity factors, can directly exert an antitumor effect on cancer cells. However, it should be noted the streptococcal vaccine should be used with caution, taking into account the individual characteristics of the patient's immune system, since S. pyogenes can also have effects of the opposite nature, requiring further research.

Онкологические заболевания остаются одной из основных причин инвалидности и смертности населения во всём мире. К наиболее злокачественным типам рака относятся опухоли поджелудочной железы, печени и головного мозга. Современные методы терапии (в том числе химиолучевая, таргетная, иммунная терапия) не позволяют добиться желаемой эффективности у этой группы пациентов. В этой связи необходимы новые подходы для терапии онкологических заболеваний.

Целью обзора явилось обсуждение механизмов противоопухолевого действия Strepococcus pyogenes и других видов стрептококков, а также рассмотрение их опухольстимулирующих эффектов и существующих при этом ограничений.

В обзоре рассмотрено современное состояние проблемы использования бактериальной онкотерапии с участием стрептококков группы А (в частности, S. pyogenes). Обсуждается участие факторов патогенности S. pyogenes: М-белка, экзотоксинов: стрептолизинов S, О, суперантигенов, аргининдеиминазы и др., а также молекулярные механизмы, опосредованные клетками иммунной системы организма-носителя. Собственные данные авторов показывают, что для S. pyogenes обнаружена селективная опосредованная М-белком цитолитическая активность в отношении опухолевых клеток глиомы С6 и аденокарциномы поджелудочной железы и её отсутствие на нормальных фибробластах. Кратко суммируются данные по доклиническому и клиническому применению полученного на основе стрептококков препарата OK-432 для терапии онкологических заболеваний. Обсуждаются и опухоль-ассоциированные свойства стрептококков (индукция секреции цитокинов, пролиферации, миграции и ангиогенеза эпителиальных клеток сосудов, образование внеклеточных ловушек нейтрофилов из микроокружения опухоли), обусловленные их взаимодействием с клетками иммунной системы организма-опухоленосителя.

Заключение. Представленные в обзоре научные данные убедительно показывают, что S. pyogenes могут при участии факторов патогенности непосредственно оказывать противоопухолевое действие на раковые клетки. Однако стрептококковую вакцину следует применять с осторожностью, учитывая индивидуальные особенности иммунной системы пациента, поскольку S. pyogenes могут оказывать и эффекты противоположного характера, требующие дальнейших исследований.

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