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Toll-like receptor 5 (TLR5) controls endogenous immune responses to pathogens and is a promising target for pharmacological stimulation of anti-tumor immunity. Mobilan is an innovative gene therapy agent consisting of a non-replicating bicistronic adenovirus directing constitutive expression of human Toll-like receptor 5 (TLR5) and the secreted flagellin-based TLR5 agonist, 502s. In mice, Mobilan injection into prostate tumors resulted in autocrine TLR5 signaling, immune system activation, and suppression of tumor growth and metastasis. Here we report a first-inhuman placebo-controlled clinical study of Mobilan aimed at evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of a single intra-prostate injection of Mobilan in early stage prostate cancer patients. Mobilan was safe and well-tolerated at all tested doses; thus, the maximum tolerated dose was not identified. Injection of Mobilan induced signs of self-resolving inflammation not present in placebo-injected patients, including transient elevation of PSA and cytokine (G-CSF, IL-6) levels, and increased lymphoid infiltration in prostate tissue. The highest dose of Mobilan (10 11 viral particles) produced the best combination of safety and pharmacodynamic effects. Therefore, Mobilan is well-tolerated and induces the expected pharmacodynamic response in humans. These results support further clinical development of Mobilan as a novel immunotherapy for prostate cancer.

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The doping of hydroxyapatite with various substituent ions can give this material new and useful properties. Nonetheless, local distortions of structure after doping can change the properties of the material. In this work, the thermal stability of copper-substituted hydroxyapatite synthesized by the mechanochemical method was investigated. In situ diffraction analyses showed that copper ion diffusion during the heating of Cu-substituted hydroxyapatite promotes phase transformations in the substituted hydroxyapatite. The behavior of copper ions was studied in samples with ratios (Ca + Cu)/P = 1.75 and 1.67. It was found that in both cases, single-phase Cu-substituted hydroxyapatite with the general formula Ca10−xCux(PO4)6−y(CO3)y(OH)2−yOy is formed by the mechanochemical synthesis. When heated at approximately 600–700 °C, the lattice loses copper cations, but at higher temperatures, CuO diffusion into the hydroxyl channel takes place. Cuprate-substituted hydroxyapatite with the general formula Ca10(PO4)6(OH)2−2x(CuO2)x forms in this context. At 1200 °C, the sample is single-phase at (Ca + Cu)/P = 1.75. Nonetheless, slow cooling of the material leads to the emergence of a CuO phase, as in the case of (Ca + Cu)/P = 1.67, where the material contains not only CuO but also Cu-substituted tricalcium phosphate. In the manufacture of ceramic products from Cu-substituted hydroxyapatite, these structural transformations must be taken into account, as they alter not only thermal but also biological properties of such materials.

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В статье отражены вопросы эпидемиологии, этиопатогенеза и классификации хронического тонзиллита. Последовательно рассматриваются современные методы лечения, в частности использования препарата Тонзилотрен в схемах терапии. Приводятся результаты международных многоцентровых рандомизированных контролируемых клинических исследований, целью которых являлось определение и оценка эффективности и переносимости препарата Тонзилотрен. Сделаны выводы о том, что Тонзилотрен является эффективным, современным средством для патогенетического лечения больных с хроническим тонзиллитом, и он может быть рекомендован в современной схеме лечения хронического тонзиллита.

Preclinical safety evaluation is an important stage in the development of medicinal products. Clinical laboratory studies, including haematological, biochemical and pathomorphological studies, are an essential part of chronic toxicity studies. A careful choice of methodological approaches to examination of toxicological characteristics of drug candidates makes it possible to assess the degree of risk associated with their subsequent clinical use, identify potential target organs, determine the extent of damage, as well as the possibility and dynamics of restoring damaged systems. Key prerequisites for obtaining adequate results of the studies are correct methodological implementation of all the stages of sample preparation and careful consideration of all factors during interpretation of the obtained data. Thus, the choice of methodological approaches to blood tests is often determined by the species, age and sex of laboratory animals, as well as by specific characteristics of the tested drug. The aim of the study was to summarise data on haematological studies performed in the Drug Toxicology Laboratory of the Federal State Budgetary Institute «Zakusov Institute of Pharmacology» when conducting chronic toxicity studies.