Novel chimeric monoclonal antibodies that block fentanyl effects and alter fentanyl biodistribution in mice
Bhupal Ban,
Rodell C. Barrientos,
Therese Oertel,
Essie Komla,
Connor Whalen,
Megan Sopko,
Yingjian You,
Partha Banerjee,
Agnieszka Sulima,
Arthur E. Jacobson,
Kenner C. Rice,
Gary R. Matyas,
Vidadi Yusibov
Affiliations
Bhupal Ban
Pharmaceutical Center, Indiana Biosciences Research Institute, Indianapolis, Indiana, United States
Rodell C. Barrientos
Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
Therese Oertel
Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
Essie Komla
Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
Connor Whalen
Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
Megan Sopko
Pharmaceutical Center, Indiana Biosciences Research Institute, Indianapolis, Indiana, United States
Yingjian You
Pharmaceutical Center, Indiana Biosciences Research Institute, Indianapolis, Indiana, United States
Partha Banerjee
Pharmaceutical Center, Indiana Biosciences Research Institute, Indianapolis, Indiana, United States
Agnieszka Sulima
Department of Health and Human Services, Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States
Arthur E. Jacobson
Department of Health and Human Services, Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States
Kenner C. Rice
Department of Health and Human Services, Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States
Gary R. Matyas
Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States
Vidadi Yusibov
Pharmaceutical Center, Indiana Biosciences Research Institute, Indianapolis, Indiana, United States
The prevalence and societal impact of opioid use disorder (OUD) is an acknowledged public health crisis that is further aggravated by the current pandemic. One of the devastating consequences of OUD is opioid overdose deaths. While multiple medications are now available to treat OUD, given the prevalence and societal burden, additional well-tolerated and effective therapies are still needed. To this point, we have developed chimeric monoclonal antibodies (mAb) that will specifically complex with fentanyl and its analogs in the periphery, thereby preventing them from reaching the central nervous system. Additionally, mAb-based passive immunotherapy offers a high degree of specificity to drugs of abuse and does not interfere with an individual’s ability to use any of the medications used to treat OUD. We hypothesized that sequestering fentanyl and its analogs in the periphery will mitigate their negative effects on the brain and peripheral organs. This study is the first report of chimeric mAb against fentanyl and its analogs. We have discovered, engineered the chimeric versions, and identified the selectivity of these antibodies, through in vitro characterization and in vivo animal challenge studies. Two mAb candidates with very high (0.1–1.3 nM) binding affinities to fentanyl and its analogs were found to be effective in engaging fentanyl in the periphery and blocking its effects in challenged animals. Results presented in this work constitute a major contribution in the field of novel therapeutics targeting OUD.
