Abstract
Introduction. Tumor necrosis factor α (TNF-α) is a natural cytokine, characterized by pronounced antitumor properties. A wide range of side effects serves as an obstacle for the use of TNF-α in clinical practice. One of the ways to improve its therapeutic properties is to increase the tropism of the cytokine to the tumor tissue by incorporating it into the targeted delivery system.The aim of the study was to evaluate the antitumor activity of the preparation containing TNF-α as part of the artificial “virus-like particle” (VLP-TNF-α), developed in SRC VB “Vector” as a transport system for delivering proteins to target cells.Materials and methods. The antitumor effect of VLP-TNF-α preparation was evaluated in experimental B16F10 melanoma model by the change of dynamics of tumor growth (volume, mass) and its morphological structure (presence of necrotic processes, blood vessel destruction). The number of the effector immune cells (CD3+, CD11b+) in the tumor tissue was determined by immunohistochemical method.Results. It has been shown that VLP-TNF-α administered intravenously at the doses of 5 × 104 and 1 × 105 IU/mouse inhibits the growth of the primary tumor. The most pronounced and stable effect was observed with a five-fold administration at the dose of 1 × 105 IU/mouse every other day: tumor growth inhibition was 40 % on the 1st day, and 47 % on the 7 th day upon the treatment. Injections of the preparation resulted in the increase of necrosis number, destruction level of the tumor tissue, development of damage and destruction of the tumor blood vessels and its infiltration with immunocompetent cells.Conclusion. The obtained data indicates that TNF-α within the delivery system exerts antitumor activity, which suggests the possibility of its further use for the treatment of malignant neoplasms, in particular, melanoma.The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.
Highlights
A wide range of side effects serves as an obstacle for the use of Tumor necrosis factor α (TNF-α) in clinical practice
The antitumor effect of VLP-TNF-α preparation was evaluated in experimental B16F10 melanoma model by the change of dynamics of tumor growth and its morphological structure
It has been shown that VLP-TNF-α administered intravenously at the doses of 5 × 104 and 1 × 105 IU / mouse inhibits the growth of the primary tumor
Summary
Фактор некроза опухоли α (ФНО-α) – природный цитокин, обладающий выраженными противоопухолевыми свойствами. Противоопухолевый эффект ВПЧ-ФНО-α исследовали на экспериментальной модели меланомы мышей B16F10 по изменению динамики роста опухоли (объем, масса) и ее морфологической структуры (наличие некротических процессов, деструкции сосудов). ВПЧ-ФНО-α при внутривенном введении в дозах 5 × 104 и 1 × 105 МЕ / мышь замедлял рост первичной опухоли. Наиболее выраженный и стабильный эффект был отмечен при 5‐кратном введении препарата в дозе 1 × 105 МЕ с интервалом 1 день: торможение роста опухоли составляло 40 и 47 % через 1 и 7 сут после окончания введения соответственно. Инъекции препарата вызывали увеличение степени деструкции опухолевой ткани и нарастание некротических изменений, повреждение и разрушение кровеносных сосудов опухоли, ее инфильтрацию иммунокомпетентными клетками. Полученные данные свидетельствуют о противоопухолевой активности препарата ФНО-α в средстве доставки, что позволяет предполагать возможность его применения в дальнейшем для лечения злокачественных новообразований, в частности меланомы. Danilenko1 1Institute of Medical Biotechnology of the State Research Center of Virology and Biotechnology Vector of the Rospotrebnadzor;
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