Generation of Polyclonal Catalytic Antibodies Against Cocaine Using Transition State Analogs of Cocaine Conjugated to Diphtheria Toxoid.

Basmadjian, Garo P.; Singh, Satendra; Sastrodjojo, Budiono; Smith, Blaine T.; Avor, Kwasi S.; Chang, Fengchun; Mills, Stanley L.; Seale, Thomas W.

doi:10.1248/cpb.43.1902

Cited by 26 publications

(12 citation statements)

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“…The cocaine molecule has several positions where linkers may be conveniently attached: the nitrogen, the methyl ester, and the benzoic acid ester. In the 1990s, there was interest in generating catalytic antibodies against cocaine which would hydrolyze the benzoic acid moiety of cocaine to give the inactive metabolite ecgonine methyl ester [Landry et al 1993;Chandrakumar et al 1993;Basmadjian et al 1995;Yang et al 1996;Berkman et al 1996]. Landry and coworkers showed that such catalytic antibodies were effective against cocaine's effects in rats [Mets et al 1998;Deng et al 2002].…”

Section: Cocaine Vaccinesmentioning

confidence: 99%

Vaccines against drugs of abuse: where are we now?

Kinsey

2014

Therapeutic Advances in Vaccines

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Drug addiction is a serious problem worldwide. One therapy being investigated is vaccines against drugs of abuse. The antibodies elicited against the drug can take up the drug and prevent it from reaching the reward centers in the brain. Few such vaccines have entered clinical trials, but research is going on apace. Many studies are very promising and more clinical trials should be coming out in the near future.

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Section: Cocaine Vaccinesmentioning

confidence: 99%

Vaccines against drugs of abuse: where are we now?

Kinsey

2014

Therapeutic Advances in Vaccines

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“…A second approach reported by Basmadjian and coworkers used again transition-state analogue haptens, but now polyclonal sera was examined for antibody catalysis. 11 Although cocaine hydrolysis was observed, no kinetic data was reported and no correlation was seen between titers and catalysis. Preparations of efficient catalytic antibodies that readily catalyze cocaine’s degradation, to a great extent, rely on the design of the transition state moiety embedded within the hapten used for imumnization.…”

Section: Introductionmentioning

confidence: 99%

Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

et al. 2013

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Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complimentary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH was found to elicit persistent high-titer, cocaine-specific antibodies, and blunt cocaine induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges the vaccine’s protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.

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“…Outside the realm of infectious disease, efforts are under way to develop catalytic antibody therapies for cocaine addiction and Alzheimer's disease (AD). The psychoactive and addictive properties of cocaine have led researchers to develop inhibitory therapies, including the use of cocaine-hydrolyzing antibodies (69)(70)(71)(72). A recent therapeutic strategy that has met moderate success in mice is based on eliciting a catalytic antibody response to cocaine with a haptenic vaccine (27).…”

Section: Therapeutic Development Of Catalytic Antibodiesmentioning

confidence: 99%

Antibody-Mediated Catalysis in Infection and Immunity

2017

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The existence of catalytic antibodies has been known for decades. Natural antibodies capable of cleaving nucleic acid, protein, and polysaccharide substrates have been described. Although the discovery of catalytic antibodies initially aroused great interest because of their promise for the development of new catalysts, their enzymatic performance has been disappointing due to low reaction rates. However, in the areas of infection and immunity, where processes often occur over much longer times and involve high antibody concentrations, even low catalytic rates have the potential to influence biological outcomes. In this regard, the presence of catalytic antibodies recognizing host antigens has been associated with several autoimmune diseases. Furthermore, naturally occurring catalytic antibodies to microbial determinants have been correlated with resistance to infection. Recently, there has been substantial interest in harnessing the power of antibody-mediated catalysis against microbial antigens for host defense. Additional work is needed, however, to better understand the prevalence, function, and structural basis of catalytic activity in antibodies. Here we review the available information and suggest that antibody-mediated catalysis is a fertile area for study with broad applications in infection and immunity.

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Generation of Polyclonal Catalytic Antibodies Against Cocaine Using Transition State Analogs of Cocaine Conjugated to Diphtheria Toxoid.

Cited by 26 publications

References 1 publication

Vaccines against drugs of abuse: where are we now?

Vaccines against drugs of abuse: where are we now?

Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

Antibody-Mediated Catalysis in Infection and Immunity

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