Russian Journal of Biotherapy
Theoretical and scientific-practical journal «Russian Journal of Biotherapy» is published since 2002 and it covers topical theoretical and scientific problems of biotherapy for immunological and oncological diseases. The Journal publishes original and review articles of studies of new biomarkers of cancer and immune diseases; reports of the use of biomarkers in diagnostics and therapy of tumors and disorders of the immune system; papers on the research in medicinal therapy; articles on the issues of technologies of development and performance of pre-clinical and clinical studies of new drugs and methods of anti-cancer treatment.
IF RusSCI: 0.509. H-Index: 14.
Editor-in-Chief: Mikhail V. Kiselevskiy – PhD, DSc, Professor, Head of Laboratory of Cell Immunity of FSBI “N.N. Blokhin National Medical Research Center of Oncology”, Ministry of Health of Russia, (Moscow, Russia) RusSCI, Scopus, ORCID, ResearcherID
Editorial board of the Journal includes prominent scientists who work in various areas of biotherapy.
Target reader’s audience – doctors and researchers in the field of experimental and clinical oncology, molecular biology, chemistry, pharmaceutics and pharmacology.
Current Issue
Vol 25, No 1 (2026)
- Year: 2026
- Published: 30.04.2026
- Articles: 9
- URL: https://bioterapevt.abvpress.ru/jour/issue/view/53
REVIEW
Laboratory diagnostics of B-cell immunity after SARS-CoV-2 and other viral infections
Abstract
Background. The COVID-19 pandemic significantly influenced the development of clinical laboratory diagnostics and showed the importance of comprehensive study of immune status to various infectious agents, in particular to SARS-CoV-2, in addition to PCR for pathogen identification. The study of humoral immunity, based on the detection of antibodies, without determining the cellular immunity assessment does not allow to assess the immune response, which is important for detecting its intensity and prognosis of the disease during infection. Assessing the potential of memory B cells to proliferate into antibody-secreting cells and quantifying the specific antibodies secreted by them will enable evaluation of the duration of B-cell memory.
Aim. To explore the current possibilities for diagnosing cellular immunity, with a focus on the B-cell component, after SARS-CoV-2 infection and other viral infections.
Materials and methods. A review study was conducted based on data from foreign (PubMed, Oxford Medicine Online, Penn Libraries, Springer) and Russian literature (e-Library), mainly from 2020 to 2025, on the methods of determining and maintaining the duration of B-cell memory to COVID-19 after vaccination and previous infection, as well as other viral infections.
Conclusion. Finding an accessible platform and methods for the detection of specific B-cell memory to SARS-CoV-2 and other infections that can be utilized in clinical diagnostic laboratories is an important challenge at the present time. The detection of a specific memory B-cell clone would allow characterizing immune status, improving retrospective long-term diagnosis of COVID-19, evaluating the efficacy of vaccine prophylaxis and predicting the effectiveness of the antagonistic response in subsequent exposure to infection. Test systems capable of characterizing B-lymphocytes by determining the clonal affiliation of the B-cell receptor and the proliferation potential of memory B-cells for subsequent secretion of specific immunoglobulins are poorly distributed in the world and absent in Russia. At the same time, the possibility of detecting memory B-cell clones for COVID-19 and other infections, capable of rapidly synthesizing a large number of specific antibodies, is of crucial importance in the development of the disease in case of repeated contact with the pathogen.
10-18
Predictive value of the KRAS gene mutation variant and co-mutation status when using immunotherapy in patients with non-small cell lung cancer
Abstract
Background. Predicting the disease course and response to various types of drug therapy is an important aspect of treating non-small cell lung cancer (NSCLC). With the rapid development of various molecular genetic testing options, particularly next-generation sequencing, it has become possible to obtain data on a large number of genetic abnormalities simultaneously. This wealth of information on the molecular genetic characteristics of tumors has become available for analysis and subsequent synthesis of data regarding the effectiveness of specific systemic therapies in each individual case, depending on the patient’s mutation status.
Aim. To evaluate the impact of KRAS mutations, such as KRAS G12C, G12D, G12V, and G12A, as well as the most common co-mutations with KRAS, on the effectiveness of immunotherapy in the treatment of lung adenocarcinoma.
Materials and methods. Collection and analysis of data from foreign and domestic literature on the prognostic significance of the comutation status of patients with KRAS-mutated NSCLC, mainly over the past 5 years. Sources were searched in the PubMed, Cochrane Library, and eLibrary abstract databases. Detailed information on the prognostic significance of the co-mutation status of patients with KRAS-mutated NSCLC is presented. It has been shown that different KRAS mutations, along with various co-mutations, have different impacts on the efficacy of immunotherapy, making expanded genetic testing of NSCLC a relevant and in-demand task with practical application.
Conclusion. Determining the co-mutation status of NSCLC patients, particularly the KRAS gene status in combination with other mutations such as TP53, STK11, KEAP1, and others, is crucial for determining sensitivity to immunotherapy and prognosticating the disease course. This field is actively developing both in Russia and internationally, demonstrating its potential and potential practical application.
19-27
Lipophilicity of drugs: general characteristics and methods of determination
Abstract
Background. Lipophilicity is one of the most significant and widely used physico-chemical characteristics of a drug, which determines its path in the body.
Aim. To systematize and generalize the literature data on the main parameters of lipophilicity and methods of its determination.
Materials and methods. The search for materials on the subject under study was carried out using the following search and information and library databases: PubMed, CyberLeninka, eLibrary, ResearchGate. The search for publications was carried out by keywords / phrases: “lipophilicity”, “lipophilicity of drugs”, “octanol / water distribution coefficient”, “assessment of lipophilicity”, etc.
Results. Lipophilicity shows the affinity of a compound to a lipophilic medium, and is traditionally expressed as the logarithm of the distribution coefficient of a molecule between two immiscible liquids − an organic solvent and water. There are various approaches to assessing lipophilicity. The standard method is “shaking in a flask”, which is based on the extraction of the test substance in the octanol-water system. Alternatively, reverse-phase thin-layer chromatography or high-performance liquid chromatography is used to assess lipophilicity. Chromatographic methods make it possible to determine the lipophilicity of a wide range of newly synthesized compounds and are characterized by low cost of experiments, simplicity and high accuracy. For ionized compounds, it is possible to use potentiometric approaches that are based on potentiometric titration or potential measurement through the use of ion-selective electrodes. Computational methods that provide quick information on lipophilicity are usually used for screening chemical libraries and have significant advantages over experimental methods. Many programs have been developed to calculate the logarithm of the distribution coefficient, which are freely available both in the form of software and on online platforms.
Conclusion. This review provides basic information about lipophilicity, describes key parameters and criteria for its assessment, and presents modern approaches to determining this characteristic.
28-40
Local delivery of chemotherapy: innovative technologies and materials for local chemotherapy platforms
Abstract
Background. Drug delivery systems are becoming an increasingly popular strategy to enhance the effectiveness of cancer treatment while reducing the systemic toxicity of chemotherapy. In recent years, the development of biomaterials and technologies for fabricating platforms (carriers) for controlled drug release has emerged as a key interdisciplinary research area at the intersection of materials science and oncology, leading to novel methods of carrier fabrication and drug incorporation.
Aim. To structure available data on the relationship between drug incorporation methods, platform fabrication techniques, and the resulting structural and functional properties of the carriers.
Materials and methods. Databases including Google Scholar, PubMed, Scopus, and ClinicalTrials.gov were used to identify and analyze studies from the past decade reporting on localized drug delivery platforms for cancer therapy. The selected studies were compared based on parameters such as porous and macrostructural morphology of the carriers, physicochemical characteristics, and controlled drug release profiles.
Results. It was found that drug release kinetics and duration depend on three main factors: the fabrication method of the carrier, its morphology (especially porosity), and the chemical composition of the polymer. Electrospinning of synthetic polymers is the most frequently applied method, enabling adjustable porosity and high specific surface area.
Conclusion. According to the reviewed studies, local drug delivery using carrier platforms contributes to an effective reduction in tumor cell proliferation and to the limitation of metastasis. This is associated with the achievement of higher and more sustained drug concentrations at the tumor site while simultaneously reducing circulating drug levels in the body, thereby decreasing systemic toxicity and increasing median overall survival. The advantages of local chemotherapy delivery, combined with technological advances, offer broad prospects for the development of safer and more effective chemotherapy strategies.
41-61
ORIGINAL REPORTS
New undifferentiated pleomorphic sarcoma cell line UPS134 for in vitro and in vivo studies
Abstract
Background. Due to the limited number of cell lines, as well as the high heterogeneity of undifferentiated pleomorphic sarcomas (UPS), the creation of new stable cell lines is relevant.
Aim. Obtaining a stable cell line from a sample of UPS obtained during surgery to model carcinogenesis processes in vitro and in vivo.
Materials and methods. Cells were isolated from a tumor sample from a patient diagnosed with UPS. After passage 40 and stable growth, the proliferation rate, cell morphology, and growth ability in 3D culture conditions were assessed. To assess tumorigenicity, the cell suspension was injected into BALB / c nu / nu athymic mice. On the 15th day of the experiment, the tumor was removed, its volume was measured, and it was examined histologically. Using short tandem repeat (STR) analysis, the cells of the resulting line were examined for the presence of human cell markers and their uniqueness. The chemosensitivity of the cells was assessed using the resazurin test.
Results. Stable growth and formation of spheroids under 3D culturing conditions were demonstrated for the cell culture. All mice inoculated with the UPS134 cell suspension showed tumor growth, and by day 14 of the experiment its average size was 28,7 mm3. Histologically, the tumor is similar in morphology to UPS, except for a smaller amount of myxoid and less polymorphism. The cells of the obtained line were shown to contain all analyzed genetic markers of human cells, and also that the STR data of the obtained line did not coincide with the STR of other lines. For doxorubicin, gemcitabine and docetaxel, IC50 (inhibitory concentration) were determined to be 15, 6.5 and 10 % of the plasma peak concentration, respectively.
Conclusions. We obtained a new cell line UPS134, which can be further used to study the pathogenesis of UPS, as well as in preclinical studies of new antitumor agents in vitro and in vivo.
62-70
Comparison of methods for assessing the immunogenicity of biological drugs based on monoclonal antibodies using the example of pembrolizumab
Abstract
Background. To ensure the safety and effectiveness of biological drugs, it is critically important to evaluate their immunogenicity. The most commonly used enzyme-linked immunosorbent assay (ELISA) has a number of limitations, so it is important to understand the possibilities of alternative approaches, for example, the biolayer interferometry (BSI) method.
Aim. Development, validation and comparison of two methods for screening assay in the context of assessing the immunogenicity of biological drugs based on monoclonal antibodies using the example of pembrolizumab with multiple intravenous administration to Macaca fascicularis.
Materials and methods. Immunogenicity was evaluated as part of a comparative study of toxicity and local tolerance of two drugs with International Nonproprietary Name pembrolizumab following repeated administration. Macaca fascicularis (3 groups of 3 males and 3 females in each) on days 1, 8, 15 and 22 of the experiment received intravenously a control substance (buffer solution), test drug (RPH-075, JSC R-Pharm, Russia) and reference drug (Keytruda®, MSD International GmbH, Ireland) at a dose 30 mg/kg. Serum samples, were collected pre-dose and on study days 15, 22, 29, and were tested for assessment of binding antibodies to pembrolizumab using two methods, bridging ELISA and BSI.
Results. During the development and testing of methods for binding antibodies (BAb) to pembrolizumab quantification in monkey’s blood serum of by the bridge ELISA and BSI assays, it was revealed that the bridge ELISA has greater sensitivity (12.3 and 419.7 ng/mL, respectively). Determination of BAb level to pembrolizumab by ELISA revealed immunogenicity in 4 out of 12 animals; when analyzing samples by BSI, an increasing of BAb concentration was detected in only one animal.
Conclusion. Bridging ELISA is more sensitive than BSI making it the preferred method for assessing of drugs with unknown or suspected low immunogenicity.
71-83
Study of acute toxicity of γ-cyclodextrin nitrates in vivo
Abstract
Background. Cyclodextrins and their individual derivatives capable of forming inclusion complexes with poorly soluble physiologically active compounds, increasing their solubility in water and slowing down their metabolism, are used as carriers of various drugs. Previously, cyclodextrin nitrates (NCD) were first proposed by us for these purposes: being organic nitrates, they can serve as a source of exogenous nitric oxide and provide an additional and independent therapeutic effect. It was found that complexes based on them exhibit synergistic antioxidant activity. A necessary stage in the study of the biological effectiveness of water-soluble NCDs, in particular, γ-NCDs, is the assessment of the safety of their use in animals.
Aim. To determine the toxic effect of water-soluble γ-NCD depending on the content of nitrate groups in an acute experiment on mice with a single intraperitoneal administration.
Materials and methods. The studies were conducted on healthy male BDF1 hybrid mice. Aqueous solutions of low-nitrated γ-NCD with nitrogen content of 2.02 % (1), 1.44 % (2) and 0.84 % (3) were administered intraperitoneally at doses of 200–600, 700–900 and 900–1300 mg / kg, respectively. Clinical signs of animal intoxication, mortality, changes in body weight, food and water consumption have been recorded for 14 days, and macroscopic examination of the internal organs of dead animals was carried out.
Results. The acute toxicity of γ-NCD 1–3 was studied experimentally with a single intraperitoneal injection to laboratory animals in the dose range of 300–600, 750–900 and 1000–1300 mg / kg, respectively. The LD50 value was established: for γ-NCD 1 it was 415 ± 33 mg / kg, for γ-NCD 2 – 800 ± 18 mg / kg, for γ-NCD 3 – 1115 ± 33 mg / kg. The results of the acute toxicity study make it possible to classify γ-NCD 1 and γ-NCD 2 to the class IV of toxicity (low-toxic substances); γ-NCD 3 to the class V of toxicity (practically nontoxic). γ-CD (gamma-cyclodextrin) with a single intraperitoneal injection in doses of 3000 mg / kg, it has no toxic effect and can be classified as toxicity class VI (relatively harmless).
Conclusion. For the first time, toxic dose levels of water-soluble low-nitrated γ-NCDs with nitrogen content from 0.84 to 2.02 % have been established, which allows them to be recommended for further research.
84-93
Lymphoid populations and tumor disseminated cells in the bone marrow in early breast cancer
Abstract
Background. The study of lymphoid populations is a necessary step for understanding the interaction between the tumor and the immune system, as well as for a detailed analysis of the persistence of tumor cells in the bone marrow of patients with breast cancer. Lymphoid populations of the bone marrow can serve as a potential point of application for immunotherapy.
Aim. To study the composition of lymphoid populations and assess the relationship with disseminated tumor cells in the bone marrow of patients with operable breast cancer
Materials and methods. The study included 65 bone marrow samples obtained by sternal puncture in patients with breast cancer. Ductal adenocarcinoma stage T1 / T2, N0 status prevailed. Luminal A was detected in 51.3 %, luminal B 10.3 %, Erb-B2 overexpressing subtype was established in 15.4 % and triple-negative subtype in 6.4 %. T cells (CD3), B cells (CD19), NK cells (CD56+CD3– ), minor populations of TCRγδ and TCRαβ lymphocytes, CD4+CD25+ T cells, subpopulations of CD10+, CD38+, CD5+ B cells were studied. CD45+EpCAM+ cells among myelokaryocytes of a bone marrow sample were assessed. An immunological study of bone marrow using monoclonal antibodies (Becton Diskinson, USA) was performed on a FACS Canto II flow cytometer. The results were analyzed using the Kaluza Analysis v.2.1 program.
Results. A relationship was established between CD19+CD10+ cells and the morphological type of breast cancer: their increased content was noted in ductal adenocarcinoma (p ≤0.05). There was a relationship between lymphogenous metastasis and the level of CD5+CD38+ cells (p ≤0.05). In high-grade cancer, there was an increase in the proportion of CD4+CD25+ cells, estrogen-positive tumors were distinguished by the predominance of NK cells in the bone marrow (p ≤0.05). T-lymphoid populations are associated with the presence of disseminated tumor cells in the bone marrow. An increase in the proportion of CD4+CD25+ with a decrease in the number of CD3+HLA-DR+ and B-cells was noted (p = 0.03).
Conclusion. Lymphoid populations of the bone marrow are associated with the morphological characteristics of breast cancer. In metastatic bone marrow lesions, the proportion of T-cell lymphoid populations changes and the number of B-cells decreases.
94-102
JUBILEE
To mark the anniversary of Valery Nikolaevich Charushin
Abstract
10 мая 2026 г. исполняется 75 лет академику Валерию Николаевичу Чарушину. Член президиума Уральского отделения Российской академии наук (УрО РАН), председатель Объединенного ученого совета УрО РАН по химическим наукам, заведующий лабораторией гетероциклических соединений, главный научный сотрудник Института органического синтеза имени И. Я. Постовского УрО РАН, профессор кафедры органической и биомолекулярной химии Уральского федерального университета имени первого Президента России Б. Н. Ельцина (УрФУ), академик РАН В. Н. Чарушин является ученым мирового уровня в области органической химии.
103-104

