دورية أكاديمية
Development of fentanyl-specific monoclonal antibody (mAb) to antagonize the pharmacological effects of fentanyl.
| العنوان: | Development of fentanyl-specific monoclonal antibody (mAb) to antagonize the pharmacological effects of fentanyl. |
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| المؤلفون: | Chen XY; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China., Wang L; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China., Ma X; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China., Yang F; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China., Wang X; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China., Xu P; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing 100193, China. Electronic address: pengxu750@163.com., Xu LL; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xulili@cpu.edu.cn., Di B; Office of China National Narcotics Control Commission, China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China. Electronic address: dibin@cpu.edu.cn. |
| المصدر: | Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 May; Vol. 486, pp. 116918. Date of Electronic Publication: 2024 Apr 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 0416575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0333 (Electronic) Linking ISSN: 0041008X NLM ISO Abbreviation: Toxicol Appl Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York, NY : Academic Press Original Publication: New York. |
| مواضيع طبية MeSH: | Fentanyl*/immunology , Analgesics, Opioid*/pharmacology , Antibodies, Monoclonal*/pharmacology , Hemocyanins*/immunology, Animals ; Mice ; Humans ; Mice, Inbred BALB C ; Male ; Respiratory Insufficiency/chemically induced ; Respiratory Insufficiency/immunology ; Tissue Distribution ; Female ; Haptens/immunology |
| مستخلص: | Fentanyl, a critical component of opioid analgesics, poses a severe threat to public health, exacerbating the drug problem due to its potential fatality. Herein, we present two novel haptens designed with different attachment sites conjugated to keyhole limpet hemocyanin (KLH), aiming to develop an efficacious vaccine against fentanyl. KLH-Fent-1 demonstrated superior performance over KLH-Fent-2 in antibody titer, blood-brain distribution, and antinociceptive tests. Consequently, we immunized mice with KLH-Fent-1 to generate fentanyl-specific monoclonal antibodies (mAbs) using the hybridoma technique to compensate for the defects of active immunization in the treatment of opioid overdose and addiction. The mAb produced by hybridoma 9D5 exhibited the ability to recognize fentanyl and its analogs with a binding affinity of 10 -10 M. Subsequently, we developed a human IgG1 chimeric mAb to improve the degree of humanization. Pre-treatment with murine and chimeric mAb significantly reduced the analgesic effect of fentanyl and altered its blood-brain biodistribution in vivo. Furthermore, in a mouse model of fentanyl-induced respiratory depression, the chimeric mAb effectively reversed respiratory depression promptly and maintained a certain level during the week. The development of high-affinity chimeric mAb gives support to combat the challenges of fentanyl misuse and its detrimental consequences. In conclusion, mAb passive immunization represents a viable strategy for addressing fentanyl addiction and overdose. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: Fentanyl; Immunotherapy; Monoclonal antibody; Opioid crisis; Passive immunization; Respiratory depression |
| المشرفين على المادة: | 0 (keyhole-limpet hemocyanin) |
| تواريخ الأحداث: | Date Created: 20240403 Date Completed: 20240519 Latest Revision: 20240519 |
| رمز التحديث: | 20240520 |
| DOI: | 10.1016/j.taap.2024.116918 |
| PMID: | 38570042 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-0333 |
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| DOI: | 10.1016/j.taap.2024.116918 |