A Method for the Production of Recombinant VSVs with Confirmation of Biological Activity.

The design of new effective cancer treatment methods is a promising and important research field in translational medicine. Oncolytic viruses can induce immunogenic cell death by activating the body's immune system to recognize tumor cells. This work presents the results for optimizing the production of recombinant vesicular stomatitis viruses (rVSVs). To ensure the assembly of viral particles, we developed the HEK293TN-T7 cell line, which stably expresses DNA-dependent RNA polymerase 7 for viral genome transcription, and obtained helper plasmids encoding viral genes under the control of the CAG promoter. The oncolytic activity of the purified virus preparation was assessed in a murine model of B16F10Red melanoma cells expressing a red fluorescent protein. The presented method makes it possible to obtain purified viral preparations with a high titer and oncolytic activity. The amplification of viral particles in a HEK293 suspension culture allows for rapid scalability. Therefore, the developed approach can be used to obtain other recombinant VSV-based oncolytic viruses for tumor immunotherapy.

Intratumor heterogeneity: models of malignancy emergence and evolution.

Cancer is a complex and heterogeneous disease characterized by the accumulation of genetic alterations that drive uncontrolled cell growth and proliferation. Evolutionary dynamics plays a crucial role in the emergence and development of tumors, shaping the heterogeneity and adaptability of cancer cells. From the perspective of evolutionary theory, tumors are complex ecosystems that evolve through a process of microevolution influenced by genetic mutations, epigenetic changes, tumor microenvironment factors, and therapy-induced changes. This dynamic nature of tumors poses significant challenges for effective cancer treatment, and understanding it is essential for developing effective and personalized therapies. By uncovering the mechanisms that determine tumor heterogeneity, researchers can identify key genetic and epigenetic changes that contribute to tumor progression and resistance to treatment. This knowledge enables the development of innovative strategies for targeting specific tumor clones, minimizing the risk of recurrence and improving patient outcomes. To investigate the evolutionary dynamics of cancer, researchers employ a wide range of experimental and computational approaches. Traditional experimental methods involve genomic profiling techniques such as next-generation sequencing and fluorescence in situ hybridization. These techniques enable the identification of somatic mutations, copy number alterations, and structural rearrangements within cancer genomes. Furthermore, single-cell sequencing methods have emerged as powerful tools for dissecting intratumoral heterogeneity and tracing clonal evolution. In parallel, computational models and algorithms have been developed to simulate and analyze cancer evolution. These models integrate data from multiple sources to predict tumor growth patterns, identify driver mutations, and infer evolutionary trajectories. In this paper, we set out to describe the current approaches to address this evolutionary complexity and theories of its occurrence.

The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells.

This review focuses on the structure and molecular action mechanisms of chimeric antigen receptors (CARs) and major aspects of the manufacturing and clinical application of products for the CAR-T (CAR-modified T lymphocyte) therapy of hematological and solid tumors with special emphasis on the strategies for combined use of CAR-T therapy with immuno-oncological monoclonal antibodies (checkpoint inhibitors) and cytokines to boost survival, persistence, and antitumor efficacy of CAR-T therapy. The review also summarizes preclinical and clinical data on the additive effects of the combined use of CAR-T therapy with interleukins and monoclonal antibodies targeting immune checkpoints.

[Comparative, placebo-controlled clinical study of efficacy and safety of glatiramer acetate 20 mg in patients with relapsing-remitting multiple sclerosis: results of the first year of the study]. / Sravnitel'noe platsebo-kontroliruemoe klinicheskoe issledovanie effektivnosti i bezopasnosti preparatov glatiramera atsetata 20 mg u patsientov s remittiruyushchim rasseyannym sklerozom: rezul'taty pervogo goda nablyudeniya.

The article presents the results of international multicenter randomized double-blind, active and placebo-controlled, comparative phase 3 trial. The goal of the study was to demonstrate non-inferiority of BCD-063 (glatiramer acetate, manufactured by JSC «BIOCAD¼, Russia) to copaxone-Teva (Teva Pharmaceutical Enterprise Co., Ltd., Israel) in patients with relapsing-remitting multiple sclerosis. METHODS: 158 patients with relapsing-remitting multiple sclerosis were randomly assigned into 3 groups: BCD-063, copaxone-Teva and placebo, at a ratio of 2:2:1, respectively. RESULTS AND CONCLUSION: Efficacy analysis after 48 weeks of therapy demonstrated no differences between BCD-063 group and copaxone-Teva group in both MRI parameters and frequency of relapses. The mean (SD) of number of MRI-confirmed relapses per patient per year (the primary endpoint) in BCD-063 group was 0.098361 (0.351422), in copaxone-Teva group - 0.098361 (0, 351 422) and in placebo group - 0.178571 (0.390021). There were also no differences between the groups for all other efficacy parameters (EDSS and MSFC). Both investigational BCD-063 and copaxone-Teva demonstrated a favorable safety profile. The data obtained from the present study confirm the therapeutic equivalence of BCD-063 (CJSC BIOCAD, Russia) and copaxone-Teva, that is important for further implementation of glatiramer acetate generic in the clinical practice of multiple sclerosis therapy.

[Influence of Different Type of Surfactant on Bacteriolytic Activity of Lysozyme].

The influence ofvarious surfactants (anionic sodium dodecyl sulfate, SDS, cationic dodecyltrimethylarnmonium bromide, DTAB, and zwitterionic cocoamidopropylbetaine, CAPB) on the activity of the chicken egg lysozyme is investigated. Lysis of Gram-positive bacteria by the enzyme was carried out at pH 7.2 and ionic strength of 0.15 M. It was found that at low SDS and DTAB concentrations (less than 1 x 10(-5) M) the bacteriolytic activity increases by 30-140%. At higher concentrations (1 x 10(-5) - 1 x 10(4) M) the activity returns to the level observed in the absence of the surfactants. The elevated activity correlated with the formation of hydrophobic lysozyme-surfactant complexes. Introduction of CAPB at concentrations above 1 x 10(-5) M sig, nificantly diminished the bacteriolytic activity due to CAPB induced aggregation of lysozyme.

Clinical and quality of life responses to high-dose chemotherapy plus autologous stem cell transplantation in patients with multiple sclerosis: two case reports.

During the last several years high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has been established as a therapeutic option for multiple sclerosis (MS) patients. We report on the long-term effects of HDCT + ASCT in two female patients affected by secondary progressive and relapsing-remitting types of MS, respectively. As a result, disease stabilization was achieved in the first case and disease improvement in the second one. Both patients were off immunosuppressive or immunomodulating therapy throughout the post-transplant period. Notably, HDCT + ASCT resulted in an excellent quality of life (QoL) response in both cases. Our findings demonstrate that HDCT + ASCT could be considered as an effective treatment for MS patients. Moreover, QoL measurement seems to be an effective approach to assessment of treatment outcomes at long-term follow-up of patients with MS.