Laboratory of Oncolytic bacteria

Head of the laboratory – Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor Alexander Nikolayevich Suvorov

MAIN GOALS OF THE LABORATORY:

  • Advanced molecular assessment of the in vitro effect of the bacterial strain GURSA on cell cultures of various human tumors (epithelial, stromal and glial) using ExCelligence technology
  • Comparison of the cytotoxic efficacy of a drug based on the GURSA strain with the effect of standard chemotherapy drugs, nerve growth factor (NGF) and cathelicidins LL37, PG-1 in a primary culture of brain tumor cells (glioblastoma, medulloblastoma) of patients.
  • Production of recombinant proteins (arginine diaminase, M-protein, erythrogenic toxins) encoded by the GURSA strain in order to assess their potential contribution to the oncolytic activity of the strain. Study of the effect of the GURSA strain and isolated recombinant proteins of this strain on the proliferative ability of tumor cells, the expression of the main factors of metastasis, angiogenesis and immunotolerance.
  • Determination of personalized sensitivity of primary cultures of brain tumor cells of patients to a drug based on the GURSA strain, comparing with the sensitivity to chemotherapy of tumor cells in a particular patient.
  • Conducting preclinical studies of the drug developed on the basis of the created strain (the presumptive name of the drug is ‘Oncolitin’) on relevant animal models, in particular, on mice with hepatoma 22a and sarcoma S37, as well as immunodeficient mice receiving injections of antigen-positive genetically engineered and linear human tumor cells.
  • Preparation of a dossier for conducting clinical trials and conducting a full-scale first phase of a clinical study in volunteers to assess the pharmacokinetics, pharmacodynamics and safety of the developed drug.

MAIN RESEARCH DIRECTION

Study of the mechanisms of the antitumor action of S. Pyogenes ”.

Development of an anticancer drug

Description of the project

Studying of the role of SHA pathogenicity factors in the effectiveness of the bacterial strain GURSA against tumor cells.

Development and description of a new domestic drug with live bacteria to protect against tumor pathology.

Research Assistants of the Laboratory

  • Head of the Laboratory – Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor Alexander Suvorov
  • Leading Researcher – Doctor of Medical Sciences, Associate Professor, Kiseleva Ekaterina Prokhorovna
  • Senior Researcher – Ph.D. in Biological Sciences, Kramskaya Tatyana Anatolyevna
  • Senior Researcher – Ph.D. in Biological Sciences, Starikova Eleonora Aleksandrovna
  • Research assistant – Nikitenko Nina Andreevna
  • Research assistant – Lebedeva Alexandra Mikhailovna
  • Junior Researcher – Dyatlova Anastasia Sergeevna
  • Research assistant – Chernov Alexander Nikolaevich
  • Junior Research – Filatenkova Tatiana Aleksandrovna

Main publications of the laboratory research assistants

  • Suvorova M.A., Kramskaya T.A., Duplik N.V., Chereshnev V.A., Grabovskaya K.B., Ermolenko E.I., Suvorov A.N., Kiseleva E.P. The effect of inactivation of the M-protein gene on the antitumor properties of living Streptococcus pyogenes in the experiment // Problems of Oncology. – 2017. – T.63, No. 5. – p. 65-69.
  • Suvorova M.A., Kramskaya T.A., Suvorov A.N., Kiseleva E.P. Inactivation of the M111 protein gene affects the interaction of Streptococcus pyogenes with mouse macrophages in vitro // Bulletin of Experimental Biology and Medicine. – 2017. – T.164, No. 9. – p. 330-334.
  • Suvorova M.A., Tsapieva A.N., Duplik N.V., Kramskaya T.A., Grabovskaya K.B., Kiseleva E.P., Chereshnev V.A., Suvorov A.N.Construction of a streptococcus strain M-protein mutant // Medical academic journal. – 2016. – Vol. 16, No. 4. – p.235-236.
  • Suvorova M.A., Kramskaya T.A., Karaseva A.B., Mukhin V.N., Ermolenko E.I., Suvorov A.N. Inactivation of the arginine deiminase gene of streptococci reduces the degree of their antitumor activity in vitro and in vivo // Medical academic journal. – 2017. – Vol. 17, No. 1. – p.96-101
  • Suvorova M., Tsapieva A., Bak E, Chereshnev V., Kiseleva E., Suvorov A., Arumugam M. Complete genome sequences of emm111 type Streptococcus pyogenes strain GUR with anti-tumor activity and it’s derivate strain GURSA1 with inactivated emm gene // Genome Announcements. – 2017. – Vol. 5, Issue 38 .– e00939-17. doi: 10.1128 / genomeA.00939-17.
  • Nikitenko, N.A. Experimental comparison of the strain of Streptococcus pyogenes serotype M111 and its mutant by mass spectrometry MALDI / N.А. Nikitenko, B.L. Milmian, N.V. Lugovkina, et al. // Problems of medical mycology. – 2018. No. 2. – S. 97.
  • Zakharenko, A.A. Disturbances of intestinal microbiocenosis in patients with colorectal cancer and methods of their correction (literature review) / A.A. Zakharenko, A.N. Suvorov, I.V. Shlyk, O.A. Ten, Sh.R. Dzhamilov, A.S. Natha, A.A. Trushin, M.A. Belyaev // Coloproctology. – 2016. – No. 2 (56). – p. 48-56.
  • Dyatlova A.S., Lin’kova N.S., Polyakova V.O., Kvetnoi I.M., Samoshkin N.G. ARID1A, PROSTAGLANDIN E2, AND ITS RECEPTOR AS POSSIBLE PREDICTORS OF MALIGNANT TRANSFORMATION OF THE ENDOMETRIUM IN ENDOMETRIOSIS. Bulletin of Experimental Biology and Medicine. 2019.Vol. 167.No. 4.P. 504-507.
  • V. Shamova, M.S. Zharkova, P.M. Kopeikin, T.A. Lukyanova, A. Yu. Artamonov, S.V. Balandin, T.A. Filatenkova, A.S. Nazarov, K.E. Safiullina, M.S. Sukhareva, T.Yu. Pazina, T.M. Grinchuk, V.N. Kokryakov, T.V. Ovchinnikova, D.S. Orlov. Proline-rich peptides of innate immunity as prototypes of new antimicrobial and antitumor drugs // Acta nature. – 2017. – Special issue. – p. 148-149
  • Pazina T.Yu., Artamonov A.Yu., Orlov D.S., Filatenkova T.A., Shamova O.V. Effects of antimicrobial peptides on the cytotoxic activity of human peripheral blood mononuclear cells against multiple myeloma cells in vitro // Medical Immunology. – 2017 .– T. 19, Special issue. – p. 51-52.
  • Nekhaeva T.L., Chernov A.N., Toropova Ya.G., Galagudza M.M., Baldueva I.A. Tumor models of mice in testing anticancer drugs. Oncology issues. 2020; 6 (4): 353-363 (RSCI, Scopus)
  • Alexander N. Chernov, Diana A. Alaverdian, Oleg S. Glotov, Michael V. Talabaev, Stanislav P. Urazov, Sergei G. Shcherbak, Olga V. Shamova. The expression of TRKA and P75 receptors and MYC-oncogenes determine the sensitivity of brain tumor cells to the treatment with the nerve growth factor in combination with chemotherapy. Drug Metabolism and Personalized Therapy. 2020; https://doi.org/10.1515/dmpt-2020-0109 (WoS, Scopus, RSCI)
  • Chernov A.N. Influence of nerve growth factor on the copy number of MYCC-, MYCN-oncogenes in human medulloblastoma cells. Malignant tumors. 2019; 1: 22-28. https://doi.org/10.18 027 / 2224-5057-2019-9-1-22-28 (RSCI)
  • Chernov A.N. Ultrastructural correlates of the mechanisms of the isolated and combined action of cisplatin, temozolomide, nerve growth factor on human astrocytoma and medulloblastoma cells. Translational medicine. 2019; 1: 28-42. https://doi.org/10.18705/2311-4495-2019-6-1-27-42. (RSCI)
  • Chernov A.N., Barantsevich E.P., Kalyunov V.N., Galagudza M.M. Methods for in vitro selection of chemotherapy drugs for individual chemotherapy of malignant neoplasms in patients. Translational medicine. 2018; 5 (3): 45–65. https://doi.org/10.18705/2311-4495-2018-5-3-45-65. (RSCI)

Patents and inventions

Patent RU 2685947 C2 from 23.04.2019 (Application 2016152829, 30.12.2016) Recombinant strain Streptococcus pyogenes (pT7ErmEMM) – tumor growth inhibitor, authors: Suvorov A.N., Chereshnev V.A., Suvorova M.A., Duplik N V., Kiseleva E. P., Gryaznova D. V., Tsapieva A. N.