Clinical trial of a humanized anti‐IL‐2/IL‐15 receptor β chain in HAM/TSP
| العنوان: | Clinical trial of a humanized anti‐IL‐2/IL‐15 receptor β chain in HAM/TSP |
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| المؤلفون: | Ashley Vellucci, Raya Massoud, Bonita R. Bryant, Joan Ohayon, Irene Cortese, Nyater Ngouth, Unsong Oh, Bridgette Jeanne Billioux, Steven Jacobson, Yoshimi Enose-Akahata, Thomas A. Waldmann |
| المصدر: | Annals of Clinical and Translational Neurology, Vol 6, Iss 8, Pp 1383-1394 (2019) Annals of Clinical and Translational Neurology |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, CD8-Positive T-Lymphocytes, Lymphocyte Activation, 0302 clinical medicine, immune system diseases, Tropical spastic paraparesis, Cytotoxic T cell, Research Articles, Interleukin-15, Human T-lymphotropic virus 1, biology, General Neuroscience, Antibodies, Monoclonal, virus diseases, Middle Aged, Paraparesis, Tropical Spastic, medicine.anatomical_structure, Interleukin 15, Cytokines, Administration, Intravenous, Female, Antibody, medicine.drug, Research Article, RC321-571, Interleukin 2, Adult, endocrine system, T cell, Neurosciences. Biological psychiatry. Neuropsychiatry, 03 medical and health sciences, Interferon-gamma, Immune system, medicine, Humans, RC346-429, Aged, business.industry, medicine.disease, HTLV-I Infections, Interleukin-2 Receptor beta Subunit, 030104 developmental biology, Immunology, biology.protein, Interleukin-2, Neurology (clinical), Neurology. Diseases of the nervous system, Nervous System Diseases, business, 030217 neurology & neurosurgery, CD8, T-Lymphocytes, Cytotoxic |
| الوصف: | Objective Human T cell lymphotropic virus 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neurological disease. Chronic activation of CD8+ T cells, as evidenced by increased spontaneous lymphoproliferation and HTLV‐1‐specific cytotoxic T cells, has been demonstrated in HAM/TSP patients. Since IL‐2 and IL‐15 stimulate memory CD8+ T cell activity, these cytokines have been implicated in the immunopathogenesis of HAM/TSP. In this phase I trial, we evaluated the safety, pharmacokinetics, and ability of Hu‐Mikβ1, a humanized monoclonal antibody directed toward the IL‐2/IL‐15 receptor β‐chain (IL‐2/IL‐15Rβ: CD122), to saturate CD122 and regulate abnormal immune responses in patients with HAM/TSP by inhibition of IL‐15 action. Methods Hu‐Mikβ1 was administered intravenously at doses of 0.5 mg/kg, 1.0 mg/kg, or 1.5 mg/kg in a total of nine HAM/TSP patients. Five doses of Hu‐Mikβ1 were administered at 3‐week intervals. The clinical response was evaluated using standardized scales. Viral and immunologic outcome measures were examined including HTLV‐1 proviral load, T cell phenotypic analysis and spontaneous lymphoproliferation in HAM/TSP patients. Results There was no significant toxicity associated with Hu‐Mikβ1 administration in HAM/TSP patients. Saturation of CD122 by Hu‐Mikβ1 was achieved in five out of nine HAM/TSP patients. Administration of Hu‐Mikβ1 was associated with inhibition of aberrant CD8+ T cell function including spontaneous lymphoproliferation and degranulation and IFN‐γ expression, especially in HAM/TSP patients that achieved CD122 saturation. Interpretation The treatment with Hu‐Mikβ1 had a number of immunological effects on HAM/TSP patients although no clinical efficacy was observed. We also did not see any dose‐related toxicity. |
| اللغة: | English |
| تدمد: | 2328-9503 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22700b7405237f5b2f2dd1b39b2fdc93 https://doaj.org/article/c31238f4eb5643fcb7a998a29c16f641 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....22700b7405237f5b2f2dd1b39b2fdc93 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23289503 |
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