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The aim of this research is to investigate the features of staphylococcal microflora of sportsmen of different specializations.

Purpose of the study: to analyze characteristics of cancer-testis antigens (Ctas) as potential biomarkers for dissemination of primary human skin melanoma (sm).Material and Methods. Recent publications from Pubmed, scopus and elibrary databases were analyzed for the available appropriate literature review. In total, 176 papers reported the description of Ctas and encoding genes and their potential for prognosis of primary sm dissemination. The authors included 52 of them in the given review.Results. Two sections of the paper comprise clinically significant characteristics of Ctas and their genes, including overexpression, which is selective for the heterogeneous tumor cell populations and mediated by humoral and/or cellular immune reactions; the association of tumor process and activation of Cta genes by demethylation of promotor sites, which is correlated with tumor progression; and the conditions required for effective immunotherapy involving Ctas and/or their genes.Conclusion. At present, there are no standards or clinical recommendations for the Cta-based prognosis of the early dissemination of primary skin melanoma. Therefore, it is important to study and analyze the Cta and encoding gene characteristics that reveal the connection between primary sm progression and tumor genesis including the role of circulating tumor cells (ctc), similar to stem cells, which have epithelial-mesenchymal transition (emt) phenotype, for clinical diagnostics of early sm dissemination. As a result of the study, the following Ctas could be considered as significant biomarkers of the early sm dissemination: mage-a1, mage-a4 and ny-eso-1, which expression correlates with the clinical pathological description of the disease progression, as well as with the relapse-free period and overall survival of the patients; magea3, which expression correlates with spag5 activation and Cd8+ t-cell abundance; ssx, a marker for stem cell migration including identification of the cells with emt and/or ctcs; and prame, signaling marker for dissemination of the uveal melanoma.

Imatinib mesilate is a well-known antitumor target inhibitor of protein tyrosine kinase, which is effective in different cancer types expressing Bcr / Abl and, in particular, in hemoblastosis. A higher interest to imatinib during the COVID-19 epidemic is explained by the fact that cancer patients are one of the COVID-19 risk groups. Moreover, imatinib target mechanism of action, which is effective in cancer, can have a high potential against the most severe COVID-19 complication such as the disease associated pulmonary fibrosis. COVID-19 associated interstitial pulmonary fibrosis develops as an autoimmune process caused by systemic inflammation with atypical (idiopathic) pneumonia resulting from acute respiratory distress syndrome with the tyrosine kinase mechanism of signaling pathway activation and cellular response. Experi-mental and clinical results showing antifibrotic and dose-related antithrombotic imatinib effect demonstrate perspective use of this antitumor agent to correct COVID-19 associated pneumonia causing a high death rate of patients with COVID-19.The review presents literature data of 2001–2020 discussing pathologic genetic and clinical characteristics of the fibrosis which exacerbates COVID-19 pneumonia in adults. The sequence of the disease processes demonstrates that disease progression with the decreasing oxygen saturation in the peripheral blood intensifies local thrombosis in the lungs. As a result, hypoxia is developing, which is difficult to control and can cause lethal outcome in severe cases. Yet, the conventional antifibrotic and thrombolytic agents can only partially control the process of pneumofibrosis including that of cancer patients. The approximate antifibrotic dose of imatinib 400 mg / day is therapeutic for oncopatho-logy. The antitumor drug registered in many countries and well described side effects and contraindications needs no long-term registration studies for a new indication, therefore, it may be easily prepared for clinical testing.

Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutininactivated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy.

Ability of mesenchymal multipotent stromal cells (MSCs) to differentiate into several types of mesenchymal tissues allows to consider these cells the main candidates for creating tissue engineering constructions for regenerative medicine. MSCs promote integration of bio-implants into the native bone and stimulate osteogenesis. MSCs are characterized by immunomodulatory properties, due to inflammation control and modification of immune cells. MSCs affect not only the in vivo immune response by preventing immunological rejection of implanted tissue engineering designs, but it can also influence the bone tissue immunity. MSCs play an important role in bone regeneration, by regulating the osteoblastic generation, and suppressing activity of inflammation effectors and osteoclastogenesis. Some pre-clinical and first clinical trials of bone bio-implants colonized with MSC, demonstrate promising outlooks for this strategy in order to obtain tissue engineering constructions for bone regeneration.

The article describes general principles of evidence-based quality assessment research of a recombinant granulocyte colony stimulating factor preparation (G-CSF) under development as well as a confirmation of its similarity to reference preparation (authorized original preparation). Since the quality of biotech preparations is determined by the manufacturing process, when developing a biosimilar one should focus on the manufacturing process details, starting from the selection of the expression system, the composition of excipients, on to the methods of isolation and purification of recombinant protein. Recombinant protein should be characterized in more details, than the quality parameters of the original preparation, included in the specification of the substance or the preparation. Comparative studies include characterization of the active substance and the assessment of the quality of the finished product. The reference preparation in the development of a biosimilar G-CSF

Intestinal mucosa is a barrier, preventing bacteria and it’s derivate from penetrating to organism, where it triggers inflammation. In this study the dynamic of intestinal permeability in cancer and cardio surgery patients during perioperative period is evaluated using dual sugar test (lactulose-mannitol). Lactulose and mannitol excretion ratio is increased in group of cancer patients with postoperative complications before and after surgery. This indicates an increased intestinal permeability in these patients. Probably increased permeability cause bacterial lipopolysaccharide translocation into blood, where it induces effectors of innate immunity, leading to system inflammation reaction due to already activated immunity. According to this, evaluation of intestinal permeability can be considered as a prognostic factor of unfavorable early postoperative period in cancer patients.

In recent years, there is a persistent increase in the spread of community-acquired infections and medical care associated infections, the cause of which is S. aureus. Previously using liquid chromatography in combination with mass spectrometry (LC-MS) analysis, spectrum of having protective activity S. aureus № 6 proteins with a molecular weight of 30 - 50 kDa, secreted into the culture medium at the end of the exponential growth phase, was investigated. 11 proteins were identified from indicated peptides and preliminary results of the protective activity of the secreted protein-based substances (SPS), marked as «initial», were obtained. While its fractionation with ion exchange chromatography on DEAE-Sepharose, the protective fraction - II SPS - was obtained. Its hypodermic immunization leads to reduction of kidney inoculation, and to kidney abscess formation, compared to the control, during the generalized infection of mice BALB/c, developing as a result of retro-orbital injection of sublethal dose S. aureus. Aim. investigation the protective extracellular proteome II SPS S. aureus № 6. Material and methods. LC-MS analysis of the received data was carried out by comparing the detected mass-spectrum protein IISPS with the results of proteomic study of the virulent strain of S. aureus Newman widely used in researches. More than 100 interacting protein clusters were identified for certain using various databases. Results. During analysis main attention was paid to 46 identified proteins involved in various biological processes. Thus, the largest group (19 proteins) is composed of carbohydrate metabolism enzymes, eight of which are involved in key stages of glycolysis; 6 proteins are related to pathogenicity factors (including clamping factors A and B, gaptoglobin-adhesive surface protein) and 4 proteins are related to stress ones. The remaining 17 proteins represent a large group of proteins involved in various metabolic and biosynthetic processes. Conclusion. The received results confirmed the data of other researchers on the identification of a large number of secreted proteins of S. aureus and on their low coincidence with secreted from clinical isolates. This demonstrates the validity of the postulate of the plasticity of the S. aureus genome affecting the exoproteome profile that largely determines the difficulties in creation of effective anti-staphylococcal vaccines.

This paper analyzes large amounts of literature data on studies of the efficiency of neoadjuvant chemotherapy (NCT) for advanced ovarian cancer (OC), which is performed prior to standard surgery. Clinical trials have demonstrated that a NCT regimen followed by cytoreductive surgery is less effective than primary cytoreductive one; however, evidence for the benefit of NCT is lacking so far. The authors conducted investigations using the intraoperative material obtained from 17 patients with T3a–cNxM0 OC, who were divided for a comparative examination into 2 groups. Group 1 included OC patents who received NCT; Group 2 comprised OC patients who did not. The tumor cells obtained from the intraoperative material of both groups were able to generate a well-proliferating culture in in vitro experiments. The cultured OC cells were characterized, by analyzing cytological specimens and the functional activity of these cells. It was ascertained that 35 % of the cultured tumor cells from OC retained their resistance to the cytotoxic action of effector cells (autologous lymphocytes) at a target cell/effector cell ratio of 1:5. Thus, both the literature and the experiment provide no unambiguous evidence supporting the fact that NCT before cytoreductive surgery is a better approach than primary surgical treatment. The optimal regimen of NCT, which would be able to enhance its efficiency, remains important.

Difficulties in the therapy of infection, caused by S. aureus, depends on the resistance of staphylococci to antibiotics, proceeding to chronicity of the diseases and the development on that background the depression of innate immunity functions and decreasing of the host resistance to the infection. In spite of tremendous efforts of researchers, up to date there are no commercial antistaphylococcal vaccine the efficacy of which would be proved in the completed clinical trials.Aim: obtaining secreted protein-based substances of the S. aureus № 6 and investigation their immunogenicity.Material and methods. Secreted protein-based substances (SPS) were obtain as: «initial» – from the filtrates of the culture fluid of the S. aureus № 6, grown to the end of the exponential phase according to the technology described previously [9], and I SPS and II SPS – after the ion-exchange chromatography of the «initial» SPS on the columns with Q-Sepharose and DEAE-Sepharose. The level of specific IgG antibodies in sera of immunized rabbits and mice determined in ELISA, the immunogenic activity evaluated in experiments of active and passive protection from the challenge performed on BALB/с mice and also by the determination of the bacterial content in organs and in the test of abscesses formation in kidneys. Results. Investigated SBS possessed the antigenic activity (the level of specific IgG antibodies in sera of immunized animals increased 2.2 – 7.5 times compared to the control groups), that is favor of the activation of the adaptive immunity system and significant protective activity revealed in experiments of active (index of efficacy 2.63 – 4.28) and passive protection. The immunization of mice with the «initial» and II SPS led to significant decrease of the number of colonyforming units of S. aureus and formation of abscesses in kidneys of mice. It is evidently, that investigated SPS, influence on the severity of staphylococcal infection and possesses the therapeutic effect.Conclusion. The preformed complex analysis at the current stage allowed to reveal perspectives of the further study of «initial» and II SPS in pre-clinical trials, as candidates, possessing the high protective facilities, for including them in the drug composition for immune prophylaxis and immunotherapy of diseases, caused by S. aureus.

More and more data suggest that ovarian cancer (OC) is an immunogenic tumor. Clinical trials dealing with immunotherapy based on activated natural killer (NK) cells and dendritic cells (DC) are under way. Mononuclear cells (MNCs) from both peripheral blood and lymph nodes (LN) are proposed to be used as a source of immunity effectors. This paper characterizes peripheral blood and LN effector cells in patients with OC. The peripheral blood displayed T cell subpopulations: T helper cells, cytotoxic T lymphocytes, and NK cells. LN showed virtually no expression of NK cell antigens, but exhibited the expression of markers of DC and T regulatory cells at the same time. The cytotoxic activity of MNCs against autologous tumor cells was higher than that against the K562 cell line. OC tissue samples were observed to contain low tumor-infiltrating lymphocyte counts.

Intrapleural immunotherapy for metastatic pleurisies demonstrates a high efficiency in the treatment of patients with breast cancer (BC). This immunotherapy modality is regarded as one of the stages of complex treatment in patients with disseminated BC and allows its capabilities to be extended for their further management.

Malignant peritoneal effusions often arise in patients with of ovarian cancer. They are dangerous complication of cancer. Intraperitoneal chemotherapy isn’t always effective and causes side effects. Intraperitoneal interleukin-2 (IL-2) and IL-2 / lymphokine activated killers (LAK) biotherapy is characterised of high efficacy in ovarian cancer patients with malignant peritoneal effusions. The objective effect was 82,6 % аnd 72,0 % accordingly. These results suggest that intraperitoneal biotherapy allows to expand possibilities of malignant peritoneal effusions treat- ment in ovarian cancer patients.

Morphology, topography, and immunohistochemical features of leukocyte infiltrates were studied in various sites of the liver samples from the patients with metastatic disease, been affected by hepatitis B and C viruses at different degree of activity. Liver of СВА mice with implanted САО-1 tumour was also under study. Histochemical, and functional features, as well as immune phenotype of these cells were investigated. It has been shown that the major fraction of leukocyte infiltrates, mostly associated with implanted tumours in experimental mice, and in the areas adjacent to the tumor in humans, like as on the peak of viral hepatitis activity, is composed of lymphocytes. They are presented by large numvers of activated proliferating and differentiating cells bearing specific antigens, as well as natural killers and T-lymphocytes, possessing high-level killer activity towards NK-sensitive, and autologous lines of cancer cells. Hence, the results of our study, generally, confirm the data from literature reporting on existence of a special lymphocyte subpopulation, NKT cells, in human or murine liver affected by hepatitis virus or malignant tumors. The data concerning functional properties of these cells may be used for development of immunotherapy methods of viral diseases and oncological conditions complicated by liver metastases.

Immunomodulating ability of a bacterial preparation (Immunovak VP-4 vaccine), and a compound of eukariotic origin (profetal), the main active component of human α-fetoprotein were under investigation in present study. Culturing of mononuclear leukocytes with the immunomodulatory factors promotes quantitative increase of the cells that express surface antigens specific for cytotoxic lymphocytes, natural killers and natural killer T-cells. Both bio-active preparations possess an expressed anti-cancer effect in vitro, i.e., they induce activation of killing properties of human peripheral blood mononuclear leukocytes, which is accompanied by acquiring their characteristic phenotype.

Abstract. We studied effects of Stimforte, an immunomodulatory drug of animal origin, upon mononuclear leukocytes (MLs) and morphology of lymphoid organs in the course of cyclophosphan-induced immunosuppression. It was demonstrated that Stimforte is able to correct the quantitative and subpopulational composition of splenic MLs, the structure of central and peripheral lymphopoietic tissues, as well as effector cell functions of innate immunity affected by the cytostatic drug. (Med. Immunol., 2011, vol. 13, N 2-3, pp 133-138)

The review highlights current approaches to adoptive immunotherapy in patients with malignant neoplasms of the female reproductive system.In spite of the obvious advances made by scientists of the world in treating malignant neoplasms, the existing treatment options remain insufficiently effective. To search for novel highly effective and safe treatments is an urgent problem of oncology. Adoptive immunotherapy is one of the priorities in this regard.

The aim of the study was to investigate the dynamics of serum immunoglobulins from oncological patients in the perioperative period. As a result of investigations, it was established that already at the initial stage of the intraoperative period the IgM concentration was elevated in patients' sera, and persisted up to 3 days after surgical intervention, while exceeding the values of the control group by 30—80 %. At the same time, no significant changes were detected in IgA and IgG levels of examined patients in the perioperative period. The obtained data confirm the expediency of carrying out the monitoring of immunoglobulin levels in oncological patients both in intra-, and postoperative periods and can be used for the assessment of patient's immune status and in the choice of immunocorrecting therapy strategy.

Aim. To study cytokine concentration in blood serum in spontaneous and NDV- and PGA stimulated production by peripheral blood mononuclear cells (PBMC) and contents of peripheral blood lymphocyte subpopulations when compared with severity of morphological changes of the liver in patients with chronic viral hepatitis B and C (CHB and CHC). Material and methods. A total of 37 patients entered the trial (13 with CHB and 24 with CHC). Concentrations of IFN-alpha, IFN-gamma, TNF-alpha, IL-1beta, IL-4, IL-6 in blood serum in spontaneous and NDV and PGA stimulated PBMC production, content of CD3, CD4, CD8, CD16, CD25, HLADR, CD20, CD38 subpopulations of peripheral blood lymphocytes were examined. Also, puncture biopsy of the liver by Mengini was made with subsequent estimation of the histological activity index by R. Knodell adapted to hepatitis B and C by K. Ishak. Results. Patients with CHB and CHC in minimal activity of the process and insignificant morphological changes in the liver demonstrated a significant fall of NDV induced IFN-alpha production. Patients with highly active hepatitis and maximal morphological changes in the liver had significant lowering of NDV induced production of IFN-alpha, IFN-gamma, TNF-alpha, IL-6 and PGA induced production of TNF-alpha. Conclusion. CHB and CHC patients should be examined not only with estimation of serum cytokines concentration but also NDV and PGA stimulated production of PBMC should be taken into consideration with calculation of immunoregulatory index for prognosis of the disease and choice of adequate therapy.

Aim. To study characteristics of leukocytic infiltration of the liver in patients with chronic viral hepatitis B and C (CVHB and CVHC) with consideration of hepatitis activity and fibrosis severity. Material and methods. The examination of 37 patients with CVHB (n = 13) and CVHC (n = 24) included liver puncture biopsy by Mengini, subsequent histological and morphological investigation of liver biopsy with immunohisto- and immunocytochemistry. Results. In CVHB and CVHC patients leukocytic infiltrates (LI) of the liver present primarily with T-lymphocytes (CD3+), NKT cells (CD3+CD16+CD56+), NK cells (CD16+CD56+), T-regulatory lymphocytes (CD4+CD25+), cytotoxic T-lymphocytes (CD8+). Cytotoxic lymphocytes (CD8+) and NK cells (CD16+CD56+) detected in hepatic LI of patients with chronic viral hepatitis are similar in composition with cells in hepatic tissue infiltrates in autoimmune hepatitis. We are the first to detect the complex of T-regulatory cells (CD4+CD25+)in hepatic parenchyma of these patients. This complex suppresses cellular immune response in virus elimination and damaged tissues and supports development of persistent viral infection with autoimmune component. Conclusion. The complex of T-regulatory cells (CD4+CD25+) isolated in hepatic LI evidences for existence of a morphofunctional base for autoimmune manifestations in the presence of persistent viral infection.