Репозиторий Университета

© 2020 Elsevier B.V. Background: Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab® (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors. Methods: The dye IR700 was conjugated with Miltuximab® and characterized by spectrophotometry and flow cytometry. Miltuximab®-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U-87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab®-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later. Results: Miltuximab®-IR700-mediated PIT caused 67.3–92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab®-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab®. Conclusions: PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.

© 2020 Elsevier B.V. Background: Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab® (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors. Methods: The dye IR700 was conjugated with Miltuximab® and characterized by spectrophotometry and flow cytometry. Miltuximab®-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U-87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab®-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later. Results: Miltuximab®-IR700-mediated PIT caused 67.3–92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab®-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab®. Conclusions: PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.

© 2020 Elsevier B.V. Background: Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab® (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors. Methods: The dye IR700 was conjugated with Miltuximab® and characterized by spectrophotometry and flow cytometry. Miltuximab®-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U-87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab®-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later. Results: Miltuximab®-IR700-mediated PIT caused 67.3–92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab®-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab®. Conclusions: PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.

© 2018 Medical Education. All rights reserved. The article provides a review on prevalence, phenotypes, endotypes, and the control of severe bronchial asthma. Severe asthma is a widespread, heterogeneous disease that affects 5 - 20% of patients with bronchial asthma. Prevalence of severe asthma in Russia significantly exceeds the official statistics data, therefore it is necessary to maintain a national register of patients with severe asthma. The conventional therapy for severe asthma is not always effective due to the uncontrolled course of the disease and eosinophilic airway inflammation. The identification of asthma phenotype/endotype is reasonable to develop a personalized approach to treatment. This approach allows to achieve better control of the disease and to minimize the risk of asthma exacerbations, fixed airway obstruction and adverse effects of the pharmacological therapy. The main changes in the Global Strategy for Asthma Management and Prevention (GINA, 2018) concerning severe asthma therapy are highlighted in this article. It is also emphasized that the use of monoclonal IL-5 and IgE-antibodies could contribute to successful treatment of patients with uncontrolled severe asthma. Currently, two immunobiological drugs have been registered in Russia, omalizumab (anti-IgE antibody) and reslizumab (anti-IL-5 antibody).

© 2018 Medical Education. All rights reserved. The aim of this study was pharmacoeconomic evaluation of treatment with reslizumab compared to omalizumab in severe eosinophilic asthma. Methods. The study was based on indirect comparison between omalizumab and reslizumab in patients with severe asthma using published data. Costs of treatment with omalizumab, reslizumab, combinations of inhaled corticosteroids and long-acting beta-agonists (ICS/LABA), outpatient treatment, treatment of exacerbations and adverse events were also compared. Сost-effectiveness analysis and budget impact analysis were used. Results. According to results of cost-effectiveness analysis, therapy with reslizumab dominated over therapy with omalizumab in patients with severe asthma in term of exacerbation rate requiring treatment with systemic steroids. According to results of budget impact analysis, switching of 100 patients from omalizumab to reslizumab could save RUB 51.99 million per year that corresponds to 36.6% reduction in general direct costs for treatment of severe asthma. Conclusion. The results of this study demonstrated economic advantage of reslizumab over omalizumab in patients with severe eosinophilic asthma.