Introduction. Animal models for SARS-CoV-2 infection, reproducing the clinical features of COVID-19 in humans, are important tools for studying the pathogenesis of the disease, transmission of the pathogen and are indispensable for testing antiviral drugs and vaccines. The aim of the study was to assess the virulence and tissue tropism for golden Syrian hamsters of SARS-CoV-2 strains belonging to different epidemiologically significant variants: Wuhan-like, Delta, Omicron BA.1.1 and Omicron BA.5.2. Materials and methods. Hamsters were intranasally infected with different SARS-CoV-2 strains. Virulence and tissue tropism of SARS-CoV-2 strains were assessed by comparing the dynamics of weight, viral load in organs and histopathological changes in lungs in infected and uninfected animals. Results. The Wuhan-like Dubrovka strain had the greatest virulence for hamsters, which was manifested by the development of severe pneumonia and a delay in weight gain by 14.6%, high virus content in the lungs, nasal passages and brain — 6.2, 5,9 and 3.7 lg TCID50/ml of homogenate, respectively. Presumably, it was the infection of the Wuhan-like virus of the central nervous system that negatively affected the weight and general condition of the animals. When hamsters were infected with viruses belonging to the Delta and Omicron variants, the observed minor weight loss in animals was uninformative, so indicators such as lung histopathology, viral load in the lungs, nasal passages, heart and other organs played a decisive role in assessing the virus pathogenicity. A score assessment of lung histopathology was of particular value in assessing the severity of pneumonia, since it reduced subjectivity in evaluating the results of histological examination and provided a semi-quantitative assessment of the pathological process. Conclusion. Despite the revealed lower virulence for hamsters of viruses belonging to the Delta and Omicron variants compared to the ancestral Wuhan virus, this animal model for COVID-19 retains its value for conducting preclinical trials of antiviral drugs.

Introduction.Bacteriochlorins are the most promising photosensitizers absorbing in the near-infrared spectral region. Their use can enhance the efficiency of photodynamic therapy due to the deeper penetration of radiation into the tumor.Objective to conduct a preclinical study of the photoinduced antitumor activity and biodistribution of Bacteriosens.Materials and methods.Bacteriosens is a preparation based on meso-tetra(3-pyridyl)bacteriochlorin absorbing at 747 nm. Photoinduced cytotoxicity was investigated in vitro using human tumor cells: A549, Hep 2, BT-474, MCF-7, SK-BR-3, PC3, and EJ and murine tumor cells: S37, C26, and LLC. In vivo studies were performed in mice with large and small tumors (S37, LLC, and C26).Results.In vitro investigation show that bacteriosens during optical irradiation led to the effective suppression of tumor cell growth in culture (the IC50 value varied from 0,08μМ to 1,21 μМ) and had no toxicity without exposure to light. The effective photodynamic therapy regimen using Bacteriosens in mice with inoculated small and large tumors of different genesis resulted in regression of a primary tumor node on 90–100 % of the animals in the absence of tumor recurrence within 90 days after treatment.Conclusion.Bacteriosens is a promising agent for the photodynamic therapy of small and large tumors; it can be successfully used as an alternative, organ-sparing minimally invasive treatment for malignant tumors, including prostate cancer.

The decoding of the DNA structure and development of new molecular methods of its analysis, as well as identification of specific genomic changes responsible for malignant transformation, have become the turning points in elaboration of novel anti-tumour drugs directed against molecular and genetic targets of tumor growth. Transition from empirical screening of agents inhibiting tumour cell proliferation to molecule-targeted analytical methods has raised a number of serious methodological issues regarding preclinical evaluation of novel medicines. The objective of this paper was to analyse general principles and features of preclinical efficacy and safety studies of different classes of modern anti-tumour drugs with a view to improve existing national guidelines. The paper reviews various aspects of preclinical studies of different classes of anti-tumour drugs (small molecule chemotherapy drugs, hormones and hormone antagonists, alkylating agents and antimetabolites, microbial and herbal medicines, as well as monoclonal antibodies). The article explores general principles of studying the drugs’ pharmacological activity in vitro, ex vivo, and in vivo, and evaluating their pharmacokinetic parameters. It describes various methods and models of research, summarises specific aspects of determination of genotoxicity, carcinogenicity, reproductive toxicity, mutagenicity, acute and chronic toxicity of various groups of medicines. It also lists criteria for selecting drug doses for toxicokinetic studies. The need for harmonisation of national requirements for conducting preclinical studies with the European standards entails alignment of terminology and further development of general algorithms for selecting doses and determining the necessary scope of research. The use of biomarkers in preclinical studies will make it possible to exclude inefficient compounds from further research.

Multiple myeloma (MM or plasma cell myeloma) is a heterogenous B-cell malignant tumor that typically exhibits a high recurrence rate, resistance to drugs, and molecular diversity of tumor subclones. Given the limited efficacy of standard therapy options, cellular immunotherapy featuring a chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of MM. The rational choice of a tumor target which shows high selectivity, stable expression, and biological significance is key to the successful implementation of CAR therapy. This review has summarized and analyzed data from the literature on biological properties, the features of expression, and the clinical development stages of CAR cell products for MM treatment which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences, and controlled safety systems. The analysis underscores the need for integrating the molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising the efficacy, stability, and safety of cellular therapy in the case of MM.

Introduction. Despite the end of the COVID-19 pandemic, the problem of vaccine prevention of this disease appears highly relevant. The emergence and widespread distribution of the Omicron SARS-CoV-2 variant of concern (VOC) and its sublineages has dramatically reduced the efficacy of vaccination. The possible approach to solving this problem is to develop a nasal live attenuated vaccine capable of activating humoral, mucosal, and cell-mediated immunity, providing a prolonged immune response and cross-protection against different VOCs. The aim of the study was to determine the immunization efficacy with attenuated cold-adapted Wuhan-like SARS-CoV-2 D-D2 strain against homologous and heterologous challenges. Materials and methods. The study was conducted on an animal model of coronavirus pneumonia in golden Syrian hamsters. The efficacy of immunization was assessed by comparing the dynamics of weight, viral load in organs and histopathological changes in the lungs in immunized and unimmunized animals. Results. Single intranasal immunization of golden Syrian hamsters with D-D2 strain showed its high immunogenicity: seroconversion was evident in all immunized animals. Wuhan-like D-D2 strain provides highly effective protection of hamsters against the development of productive infection and pneumonia when challenged both with ancestral virus and heterologous strains related to Delta (AY.122) and Omicron (sublineages BA.1.1 and BA.5.2) variants. Conclusion. SARS-CoV-2 attenuation is a promising strategy for the development of a highly effective nasal live COVID-19 vaccine.

Изучение общетоксических свойств препарата бактериосенс, предназначенного для фотодинамической терапии злокачественных новообразований на грызунах и крупных животных