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An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression

Eubanks, Lisa M. ; Pholcharee, Tossapol ; Oyen, David ; Natori, Yoshihiro ; Zhou, Bin ; Wilson, Ian A. ; Janda, Kim D.

ACS chemical neuroscience, 2023-08, Vol.14 (16), p.2849-2856 [Periódico revisado por pares]

United States: American Chemical Society

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  • Título:
    An Engineered Human-Antibody Fragment with Fentanyl Pan-Specificity That Reverses Carfentanil-Induced Respiratory Depression
  • Autor: Eubanks, Lisa M. ; Pholcharee, Tossapol ; Oyen, David ; Natori, Yoshihiro ; Zhou, Bin ; Wilson, Ian A. ; Janda, Kim D.
  • Assuntos: Analgesics, Opioid - therapeutic use ; Drug Overdose ; Fentanyl ; Humans ; Immunoglobulin Fragments ; Opiate Overdose - drug therapy ; Respiratory Insufficiency - chemically induced ; Respiratory Insufficiency - drug therapy
  • É parte de: ACS chemical neuroscience, 2023-08, Vol.14 (16), p.2849-2856
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: The opioid overdose crisis primarily driven by potent synthetic opioids resulted in more than 500,000 deaths in the US over the last 20 years. Though naloxone, a short-acting medication, remains the primary treatment option for temporarily reversing opioid overdose effects, alternative countermeasures are needed. Monoclonal antibodies present a versatile therapeutic opportunity that can be tailored to synthetic opioids and help prevent post-treatment renarcotization. The ultrapotent analog carfentanil is especially concerning due to its unique pharmacological properties. With this in mind, we generated a fully human antibody through a drug-specific B cell sorting strategy with a combination of carfentanil and fentanyl probes. The resulting pan-specific antibody was further optimized through scFv phage display, producing C10-S66K. This monoclonal antibody displays high affinity to carfentanil, fentanyl, and other analogs and reversed carfentanil-induced respiratory depression. Additionally, X-ray crystal structures with carfentanil and fentanyl bound provided structural insight into key drug:antibody interactions.
  • Editor: United States: American Chemical Society
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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