Russian Journal of Biotherapy
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304
(FIVE YEARS 121)

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Published By Publishing House Abv Press

1726-9784

2021 ◽  
Vol 20 (4) ◽  
pp. 66-74
Author(s):  
O. I. Tarasova ◽  
A. A. Ryzhova ◽  
M. I. Savinova ◽  
V. D. Borodin

Availability of patents for inventions is a significant indicator of innovative activity in scientific research organization, one of efficiency criterion of its work, creates legal basis for integration innovations into practice and future commercial use. Not every inventor can formulate the point of his invention and describe it correctly according to demands of current legislation.Objective is to help a beginning inventor to form description and formula of invention correctly, to provide information, necessary for giving patent’s application.Recommendations for drawing up a claim according to the patent law of Russia are present in the article with an accent on inventions in the medical area. Conditions of patentability, objects of invention, patent validity periods have been considered. Conditions of creation companies’ inventions have also been highlighted. In the article the demands to a content of applications, structure of description, formula and an abstract of invention have been disclosed in details in compliance with “The Rules of drawing up, applying and considerations of papers (documents), which are the basis for performing legally significant actions in accordance with State registration of inventions” and “Demands to documents of an application of patent of invention”, approved by the Order Minister of Economic Development of Russian Federation, dated on 25.05.2016 No. 316. The example of description of invention in the medical area is given in order to illustrate an invention prototype.According to patent legislation of Russian Federation, a protection is provided to technical decision, which is new, not evident for a specialist in a given filed and is fully revealed in description of an invention in an amount, that is enough for its reproduction, and realization of a stated purpose is confirmed by materials of application. Formula of application must be totally based on a description.


2021 ◽  
Vol 20 (4) ◽  
pp. 59-65
Author(s):  
D. S. Vorobyev ◽  
M. M. Tokarskaya ◽  
S. A. Baranovskaya ◽  
E. A. Stefutushkina ◽  
O. M. Afanasyeva ◽  
...  

Introduction. Pneumococcal diseases remain relevant for the whole world. On the one hand, this is due to the high prevalence of pneumococcus and the other hand, the growth of antibiotic-resistant strains and the constant change of clinically significant serotypes of the pathogen.The aim of the research was to study of the protective activity of a mixture of pneumococcal antigens.Material and methods. we used preparations of a capsular polysaccharide (CPS) obtained from Streptococcus pneumoniae serotype 3; protein-containing fraction (PCF) obtained from an aqueous extract of cells of S. pneumoniae serotype 6B; recombinant pneumolysin (rPly). Mice were immunized intraperitoneally twice with an interval of 14 days with mixtures of bacterial antigens: CPS + PCF; CPS + rPly; PCF + rPly. To assess the protective activity of the studied drugs after double immunization animals were infected intraperitoneally with S. pneumoniae serotype 3. To study the effect of mixtures of bacterial preparations on the infectious process in the lungs immunized mice were infected with S. pneumoniae serotype 3. The humoral immune response was studied with IgG using the method of ELISA.Results. The CPS + rPly mixture protected mice from intraperitoneal infection with S. pneumoniae serotype 3 regardless of the infecting dose. Immunization with CPS + PCF or CPS + rPly mixtures influenced a significant decrease the number of seeded bacterial cells from lungs during the entire observation period (72 h) compared to the control. Administration of mixtures of bacterial antigens of CPS + PCF, CPS + rPly or PCF + rPly to animals led to a significant increase of the level of antibodies to all antigens, however, the highest levels of IgG were determined to PCF and rPly.Conclusion. The results obtained suggest that different antigenic drugs in mixtures affect different mechanisms of immunity activation.


2021 ◽  
Vol 20 (4) ◽  
pp. 51-58
Author(s):  
A. V. Ponomarev ◽  
A. A. Rudakova ◽  
Z. A. Sokolova ◽  
M. A. Baryshnikova ◽  
V. S. Kosorukov

Introduction. It is known that the agonist of TLR-3 Poly(I:C), used as an adjuvant in a number of models of antitumor vaccines, causes inhibition of melanoma B16 growth, but the immunological aspects involved in this process have not been fully studied.The aim of the study was to evaluate changes of the immunophenotype of the spleen cells of C57BL / 6 mice caused by the tumor load and / or Poly(I:C), which is necessary for better understanding of the processes occurring during Poly(I:C) inhibition of melanoma B16-F10.Materials and methods. The immunophenotype of splenocytes of C57Bl / 6 mice was studied by flow cytometry asfollowing: the group 1 was a control (intact animals), the group 2 was mice with subcutaneously transplanted melanoma B16-F10, the group 3 was mice without a tumor treated with Poly(I:C) and the group 4 – mice with subcutaneously transplanted melanoma B16-F10 treated with Poly(I:C).Results. Median values of parameters such as the CD4 / CD8 immunoregulatory index, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells for the group of mice with melanoma treated with Poly(I:C) were between the values in the control group and in the group of mice with B16-F10. when comparing the results, the number of B and NK cells, the percentage of CD69+ on CD4+ and CD8+ T cells, their median in the group of mice with melanoma treated with Poly(I:C) was closer to the control than to the values obtained in the B16-F10 group and in the group of healthy mice receiving Poly(I:C). At the same time, we found that the total number of CD3+ cells, the number of naive CD4+ and CD8+ T cells was higher in the group of mice with melanoma treated with Poly(I:C) compared to all other groups.Conclusion. The analysis revealed the changes of the immunophenotype of murine spleen cells (CD4 / CD8, the percentage of CD69+ CD4+ and CD8+ T cells, the number of B and NK cells), which were affected by the tumor load and / or the administration of Poly adjuvant (I:C). Changes in the immunophenotype of murine splenocytes were associated with the tumor load and its size. It was also found that the splenocyte immunophenotype was affected by the repeated administration of Poly(I:C) during the tumor growth.


2021 ◽  
Vol 20 (4) ◽  
pp. 42-50
Author(s):  
O. A. Bocharova ◽  
V. B. Matveev ◽  
E. V. Bocharov ◽  
R. V. Karpova ◽  
V. G. Kucheryanu

The review presents the concept the key mechanism of the tumor process is a violation of adhesion interactions involving local and central mechanisms. Local features of adhesive dysregulation are demonstrated in the part 1. The second part describes the central processes. Features of local adhesive dysregulation which provides the main properties of the tumor (loss of tissue control of proliferation, anaplasia, invasion, metastasis, lack of immunological surveillance) can be controlled by central mechanisms involving the dopaminergic system which is able using immunoadhesional interactions to regulate the active phase of immune responses against the tumor interfering the process and thus interrupting the development of a malignant neoplasm initiated by a local mutation in the target tissue. The proposed concept of the adhesion key role dysregulation in the target tissue neoplasia and the processes of immunoreactivity involving the loss of central dopamine as an adhesive-damaging factor at the level of immune responses reveals among other things the stress mechanism of cancer etiology. At the same time, the central dopamine directly affects the level of dopamine in the peripheral body. The main reserves of peripheral dopamine in platelets and blood lymphocytes can serve as a guarantee of antitumor protection. Being the production of lymphocytes peripheral dopamine plays a role in the maturation of cytotoxic lymphocytes promoting their migration to tumor nodes, the formation of conjugates with tumor cells. So, dopamine participates in the active phase of immune responses against the tumor contributing to the support of adhesive interactions between immune effectors and target cells. The latter also helps to protect the body from tumor diseases which obviously shorten life.The adhesive concept of local and central control of tumor formation creates a certain perspective for improving the effectiveness of diagnosticis, prevention and treatment methods which can be a step towards solving the problem of malignant neoplasms.


2021 ◽  
Vol 20 (4) ◽  
pp. 26-32
Author(s):  
G. M. Volgareva

Human papillomaviruses (HPV) of the high-risk types cause carcinomas in cervix uteri, vulva, vagina, penis, anus, as well as in certain sites of head and neck – oral cavity, oropharynx, tonsils, larynx. HPV of types 16 and 18 are the most widespread ones. Papillomaviruses of low oncogenic risk, HPV of types 6 and 11, cause recurrent respiratory papillomatosis and anogenital warts. Preventive vaccinations against HPV are not included into the National mandatory immunization schedule in Russia; however, they are being executed in several country areas in a form of regional programs. Substantial contingents are not embraced by the procedures as yet. A family can make decision of its own whether to vaccinate the adolescent child on paid basis. To make decision in favor of vaccination complete awareness is needful on the HPV infection consequences. As far as viruses of the given group became primarily known as cervical cancer etiological agents certain risk persists of “feminization” of notions about unfavorable effects of the HPV infection thus resulting in debates on usefulness of boys’ preventive vaccination.In this connection the purpose of the review was consideration of HPV effects on male reproductive potential. Oncogenic HPVs are frequently found in healthy donors’ sperm. HPV DNA can penetrate from sperm into oocyte under experimental conditions. Seminal fluid of HPV-positive males is a storage tank of the virus as well as the source of its distribution throughout population. DNA of oncogenic HPV was detected in endosomes of seminal lymphocytes. The latter fact opposes the canonic notion of strict HPV epitheliotropy. Correlation exists between the seminal fluid HPV-positivity of a certain man and his fertility drop. Reproductologists believe failures of some married couples when using assisted reproductive technologies may result from partner’s seminal HPV positivity. The successful attempt is known of semen parameters’ normalization in men with reduced fertility after inoculation with the quadrivalent Gardasil vaccine.It seems reasonable to consider the data on unfavorable effects of HPV infection on male reproductive potential as an argument for boys’ preventive HPV vaccination. It would help not only to prevent the HPV-associated oncological diseases in men but the distribution of the given infection around the population as a whole; it would contribute to more successes in solving demographic problems.


2021 ◽  
Vol 20 (4) ◽  
pp. 33-41
Author(s):  
K. S. Titov ◽  
A. A. Markin ◽  
A. M. Kazakov ◽  
S. V. Chulkova

Contemporary discoveries of fundamental science in recent decades in the field of oncology have led to the emergence of new highly effective anticancer drugs: targeted drugs and immune checkpoint inhibitors, use of which has made a breakthrough in the treatment of oncological diseases, including skin melanoma. Melanoma is still one of the most cancerous tumors. The number of patients resistant to targeted therapy and immunotherapy increases in the world every year. Oncologists have practically no leverage to influence the disease after the development of resistance to this type of therapy. In this regard, scientists around the world are looking for new application points for targeted drugs. Nowadays, the most common treatment method is BRAF inhibitors, since the BRAF mutation is detected in 40–60 % of patients with skin melanoma. However, the resistance to BRAF inhibitor therapy occur in half cases after 6–8 months. To overcome the resistance to the target therapy is one the most important issue, the studying of new isoform of anaplastic lymphoma kinase (ALK) may help to solve this problem.Purpose of the study – to order the data of the leading researchers of a new isoform of ALK, and reveal the most promising directions for its further progress.In the article, there are comparisons and analyses the 6 of the largest studies over the past 5 years devoted to a new isoform of ALK.The joint inhibition of the new ALK isoform and BRAFV600 showed positive results in several studies with different levels of ALKATI expression (alternative initiation of ALK transcription). The new ALK isoform can stimulate oncogenesis only within a certain “threshold” level of expression. Immunohistochemical examination cannot be the main method for determining the expression of a new ALK isoform due to low sensitivity. In almost all studies, tumors with ALK translocation responded to therapy with ALK inhibitors.Even though that the role of the new ALK isoform has been studied in recent years, the optimal method for evaluating the expression of ALKATI in routine practice has not yet been determined. Additional studies are also needed to understand the effectiveness of the use of ALК inhibitors in combination with BRAF and ERK inhibitors. Of interest is the blockade of extracellular vesicles and the study of the role of interleukin-3 in the inhibition of ALKATI.


2021 ◽  
Vol 20 (4) ◽  
pp. 18-25
Author(s):  
E. A. Pogodina ◽  
A. V. Lobov ◽  
P. I. Ivanova ◽  
V. I. Kazey ◽  
I. Zh. Shubina

The aim of the review is studying the immune response to the new coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus in different populations, including those with immunosuppression due to concomitant diseases or immunosuppressive therapy.The role of T cells in building up the anti-COVID-19 immunity is of special interest, particularly, when comparing T cell and antibody based immunity. A number of studies are focused on the effectiveness of T-cell immunity against SARS-CoV-2 infection, as well as on the resistance to re-infection. The decreased immunity associated with such illnesses as autoimmune diseases, non-autoimmune inflammations, and the effect of immunosuppressive drugs and obviously, different cancers increase the susceptibility to SARS-CoV-2 and COVID-19 development, and exacerbate the course of the disease.Several studies showed that patients with cancer are at risk of impaired immune response associated with a malignant neoplasm. The inefficient immune response was also shown in cancer patients receiving immunomodulatory therapy. However, some studies registered the specific immunogenicity after vaccination in patients with concomitant immunosuppression.Methotrexate is a folate antimetabolite. The drug can be used both in high doses as an antimetabolite in the antitumor therapy, and in low doses as an immunosuppressive agent in patients with autoimmune diseases. Therefore, the review also discusses a study that evaluated the humoral and cellular immune response to the BNT162b2 (PfizerBioNTech) anti-COVID-19 vaccine in patients receiving methotrexate. The rate of antibody production was lower in patients receiving methotrexate, though the level of T-cell response was similar in all groups studied.The review discussed immune compromised patients with cancer and hematological malignancies and patients living with HIV who had COVID-19. Most studies reported no significant differences of COVID-19 outcomes between major population and the patients with suppressed immune system.Hereby, the cell and humoral immune response in immune compromised patients is possible, however, additional studies are required to confirm these data.


2021 ◽  
Vol 20 (4) ◽  
pp. 10-17
Author(s):  
A. V. Lobov ◽  
P. I. Ivanova ◽  
E. A. Pogodina ◽  
V. I. Kazey ◽  
E. D. Maksimova ◽  
...  

In December 2019 humanity faced a new coronavirus infection caused by SARS-CoV-2 virus and the disease referred to as COVID-19 has spread globally.Specially adapted for the detection of SARS-CoV-2 RNA tests based on polymerase chain reaction are used to identify infected patients by processing nasal and oropharyngeal swabs. However, often it may not be sufficient to use polymerase chain reaction only, but in many cases it is very important to assess the humoral and cellular immune reactions to the infection.The present review aims to summarize and analyze the available literature data on the formation of the immune response and diagnostic methods used for characteristics of the immune reactions in patients who recovered from COVID-19 or received an anti-COVID-19 vaccine.Currently, the effectiveness of anti-COVID-19 vaccination and the developing immunity after a previous illness are assessed by detecting specific antibodies. A number of observations show that anti-S and anti-RDB IgG titers significantly decline within 6–8 months after diagnosis. It is important to note that although the antibody levels in the blood of recovered patients decrease, the memory cells can be determined by the appropriate tests.The ELISPOT (Enzyme-linked immunospot) method, which is a variation of the ELISA (Enzyme-linked immunosorbent assay), allows estimation the T- and B-cells that release activation factors such as cytokines and antibodies in response to the presented antigens.The assessment of the generation and effective function of the immune memory to SARS-CoV-2 requires the evaluation of the content and functional activity of its various components, including B-lymphocytes, CD8+, CD4+T-lymphocytes, since they have rather independent mechanisms of action of cellular memory.Therefore, it is crucially important to have tools for evaluating the immunity to SARS-CoV-2 when the level of antibodies is insufficient for determination by the available registered tests, and the introduction of test systems into clinical diagnostic practice, allowing to identify markers of long-term cellular memory, are relevant.


2021 ◽  
Vol 20 (3) ◽  
pp. 17-24
Author(s):  
O. A. Bocharova ◽  
V. B. Matveev ◽  
E. V. Bocharov ◽  
R. V. Karpova ◽  
V. G. Kucheryanu

The review presents the concept the key mechanism of the tumor process is a violation of adhesion interactions involving local and central mechanisms. Local features of adhesive dysregulation are demonstrated in the first part. The lack of histospecific adhesion molecules expression resulting from stress or genetic mutation damages an important mechanism of antitumor protection of the tissue disrupting the processes of proliferation and differentiation. The deficiency of histone-specific homotypic adhesion molecules which occurs later exacerbates the disorders. This leads to a decrease in the expression of leukocyte integrins (LFA-1, Mac-1) ligands of the β2 family on the surface of immune effectors and to an increase also in the expression of adhesion molecules to the substrate-antigens VLA (very late activation) family of β1 -integrins on tumor cells. The first restricts the interaction of ICAM family molecules with their contra-receptors from the β2 -integrin family reducing the elimination of target cells by immune effectors which contributes to the screening of the tumor from antitumor surveillance. The second promotes the invasion of the tumor into the surrounding tissues, the formation of blood vessels as well as its heterotypic adhesion with other tissues which further stimulates the proliferation and suppression processes of tumor cells apoptosis. So, the adhesion molecules can be compared to the Phoenix bird: disappearing at the beginning of the process (between the similar cells), they reappear in a new quality (increasing adhesion to cells of other tissues), increasing the totalysm of the tumor. It should be taken into account that tumor cells due to adhesion dysregulation “isolate themselves from society”, lose their differentiation, their maturity and “fall into childhood”, being unable to perform specific, “adult” functions. So, cancer can be considered as a manifestation of the cells aging. Therefore, the anti-stress, endogenous geroprotective mechanisms activation based on the adhesion correction can be effective for preventing and treatment the oncological process. 


2021 ◽  
Vol 20 (3) ◽  
pp. 10-16
Author(s):  
I. Zh. Shubina ◽  
N. A. Burlaka ◽  
A. P. Kazantsev ◽  
Yu. I. Dolzhikova ◽  
A. A. Petkevich ◽  
...  

Diagnosis, treatment and designing an adequate strategy of neuroblastoma (NB) therapy in children is still a complicated tasks for pediatric oncology and hematology. One of the key aspects of NB control is detection and monitoring of minimal residual disease.The authors make a concise review of the up-to-date methods, such as immunocytochemistry, fluorescent in situ hybridization (FISH), flow cytometry, the methods of qualitative and quantitative polymerase chain reaction (PCR) to estimate mRNA (RT-PCR and QRT-PCR), which are currently used for minimal residual disease detection in patients with NB. Disialoganglioside GD2, a specific NB marker, is traditionally determined by immunocytochemistry with fluorochromes that enhance its specificity, and by flow cytometry, as well. At present, FISH test is a gold standard for evaluation of the MYCN gen status in NB. A widely used multicolor flow cytometry method allows achieving high specificity of the analysis for NB diagnosis. RT-PCR may search for various targets to reveal NB cells, however, at the moment the only accepted immune target is tyrosine hydroxylase mRNA. Moreover, the studies established that quantitative QRT-PCR has more advantages than traditional qualitative RT-PCR, since this method allows a more accurate and quantitative detection of one or several mRNAs in clinical samples. The review discusses advantages and disadvantages of the main methods currently used for minimal residual disease evaluation of NB cells, such as RT-PCR, flow cytometry, FISH, etc. Comparative studies included multicolor flow cytometry with various combinations of CD9/CD81/CD56/CD45/GD2 monoclonal antibodies, conventional RT-PCR and quantitative QRT-PCR to reveal circulating/disseminated NB cells in the clinical samples of cancer patients and healthy volunteers.The authors analyze the results of various studies that compared accuracy and sensitivity of diagnostic methods such as RT-PCR, flow cytometry, FISH and some others. Despite the advantages of each method, the authors emphasize that multicolor flow cytometry is the optimal approach for the rapid and reliable detection of minimal residual disease and micrometastases of NB. 


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