Immunotherapy for the treatment of drug abuse

Kosten, Thomas R.; Owens, S. Michael

doi:10.1016/j.pharmthera.2005.06.009

Cited by 119 publications

(127 citation statements)

References 39 publications

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“…1) to attain immediate short term (minutes to hours) or long-lasting (weeks to months) protection. Both therapies provide antibodies that act as pharmacokinetic antagonists 4 serving to sequester the drug in the vascular compartment and prevent the drug from entering various critical sites of action like the brain. 5 The key initial step for creating both passive and active immunotherapy for METH is the design of a suitable METH-like hapten.…”

Section: Introductionmentioning

confidence: 99%

Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse—Methamphetamine and 3,4‐methylenedioxymethamphetamine

Celikel¹,

Peterson²,

Owens³

et al. 2009

Protein Science

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Methamphetamine (METH) is a major drug threat in the United States and worldwide. Monoclonal antibody (mAb) therapy for treating METH abuse is showing exciting promise and the understanding of how mAb structure relates to function will be essential for future development of these important therapies. We have determined crystal structures of a high affinity anti-(1)-METH therapeutic single chain antibody fragment (scFv6H4, K D 5 10 nM) derived from one of our candidate mAb in complex with METH and the (1) stereoisomer of another abused drug, 3,4-methylenedioxymethamphetamine (MDMA), known by the street name ''ecstasy.'' The crystal structures revealed that scFv6H4 binds to METH and MDMA in a deep pocket that almost completely encases the drugs mostly through aromatic interactions. In addition, the cationic nitrogen of METH and MDMA forms a salt bridge with the carboxylate group of a glutamic acid residue and a hydrogen bond with a histidine side chain. Interestingly, there are two water molecules in the binding pocket and one of them is positioned for a CAHÁ Á ÁO interaction with the aromatic ring of METH. These first crystal structures of a high affinity therapeutic antibody fragment against METH and MDMA (resolution 5 1.9 Å , and 2.4 Å , respectively) provide a structural basis for designing the next generation of higher affinity antibodies and also for carrying out rational humanization.

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Section: Introductionmentioning

confidence: 99%

Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse—Methamphetamine and 3,4‐methylenedioxymethamphetamine

Celikel¹,

Peterson²,

Owens³

et al. 2009

Protein Science

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show abstract

“…These mAbs were then further examined for their ability to recognize substrates 2-5. Competition ELISA between BSA-7 and the panel of substrates (2)(3)(4)(5) revealed that a single mAb, YX1-40H10, could bind to (ϩ)-2 with an apparent binding constant,…”

Section: Resultsmentioning

confidence: 99%

“…1), is a serious global problem (1)(2)(3). Immunopharmacotherapy that utilizes antibody-based therapeutics is being studied as an innovative approach to controlling the abuse of these psychoactive agents (4,5). In this regard, antibody catalysts that can convert drugs of abuse into inactive forms are viewed potentially as more efficient immunotherapeutic agents than immunoglobulins that simply bind and either sequester or eliminate the drug.…”

mentioning

confidence: 99%

Antibody-catalyzed anaerobic destruction of methamphetamine

Hixon²,

Yamamoto³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Administering a preventive NV to minors has never been the subject of clinical trials, and yet, it has inspired much ethical analysis. Recurrent themes are the balance between the neurobiological, socio-economic and psychological sides of adolescent smoking (Kosten and Owens, 2005;Lev et al, 2013), the autonomy and well-being of children, including their 'right to an open future' (Hasman and Holm, 2004) and the role and obligations of parents (Feldman, 2013). Furthermore, the necessity, utility and unintended social consequences of preventive vaccination campaigns have been discussed (Gartner et al, 2012;Lieber and Millum, 2013).…”

Section: Introductionmentioning

confidence: 99%