AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

Rosenberg, Jonathan B.; Hicks, Martin; De, Bishnu P.; Pagovich, Odelya; Frenk, E.; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.; Crystal, Ronald G.

doi:10.1089/hum.2011.178

Cited by 42 publications

(35 citation statements)

References 53 publications

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“…Antibody processing and expression were found to be just as effective in vivo, as functional recombinant antibody 14F7 was detected in animal circulation just a week after rAAV injection. This is in line with previous works reporting the in vivo expression of recombinant antibodies by rAAV-mediated gene transfer in several preclinical models of viral and parasitic diseases[37][38][39] , cancer40,43 and neurological conditions41,42 .…”

supporting

confidence: 91%

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Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody

et al. 2015

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The ganglioside GM3(Neu5Gc) has gained increasing attention as therapeutic target because of its selective expression in various human tumours, such as melanoma, breast and lung cancer. 14F7 is a mouse IgG1 with specific reactivity to GM3(Neu5Gc)-positive tumours. The therapeutic activity of 14F7 has also been demonstrated in vivo, through its repetitive passive administration in tumour-bearing animals. In this work we used an alternative strategy to deliver recombinant 14F7 in vivo and analysed the therapeutic efficacy of this approach. We engineered a recombinant adeno-associated vector to direct the expression of secretable recombinant 14F7 in BALB/c animals. A single administration of the rAAV induced efficient production and secretion of the antibody in the bloodstream, with an expression level reaching plateau at ∼3 weeks after injection and persisting for almost a year. Strikingly, upon challenge with GM3(Neu5Gc)-positive X63-AG8.653 myeloma cells, tumour development was significantly delayed in animals treated with rAAV-14F7 with respect to animals treated with a control rAAV codifying for an irrelevant antibody. Finally, no significant differences in survival proportion were detected in animals injected with rAAV-14F7 or treated by standard administration of repetitive doses of purified monoclonal antibody 14F7.

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supporting

confidence: 91%

“…The in vivo expression of recombinant antibodies by rAAV-mediated gene transfer in several disease models has also been reported [37][38][39][40][41][42][43] .…”

Section: Introductionmentioning

confidence: 85%

Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody

et al. 2015

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“…Importantly, the expression of this antibody also blocked nicotine-mediated alterations in arterial blood pressure, heart rate and locomoter activity, demonstrating its ability to obviate the physiological effects of nicotine [57]. Using a similar approach against cocaine, AAVrh.10 was engineered to express the high affinity anti-cocaine mAb GNC92H2 [58], leading to the expression of anti-cocaine antibodies for at least 24 weeks after IV administration and resulting in a 31-fold reduction in the ratio of brain to blood cocaine levels and reduced hyperactivity in treated mice as compared to controls [58]. …”

Section: Vectored Antibody Delivery For Addictionmentioning

confidence: 99%

Engineering humoral immunity as prophylaxis or therapy

Deal

Balazs

2015

Current Opinion in Immunology

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Purpose of the review In this review, we will discuss the field of engineered humoral immunity with an emphasis on recent work using viral vectors to produce antibodies in vivo. As an alternative to passive transfer of monoclonal antibody protein, a transgene encoding an antibody is delivered to cells via vector transduction, resulting in expression and secretion by the host cell. This review will summarize the evidence in support of this strategy as an alternative to traditional vaccines against infection and as novel therapeutics for a variety of diseases. Recent findings Historically, humoral immunity has been engineered through vaccination and passive transfer of monoclonal antibodies. However, recent work suggests that vectors can be used to deliver transgenes encoding broadly neutralizing antibodies to nonhematopoietic tissues and can mediate long-term expression that is capable of preventing or treating infectious diseases. The production of engineered monoclonal antibodies allows for precise targeting and elimination of aberrant self-proteins that are characteristic of certain neurodegenerative disease. This approach has also been successfully used to combat cancer and addiction in several animal models. Despite the wide array of expression platforms that have been described, adeno-associated virus vectors have emerged as the frontrunner for rapid clinical translation. Summary Recent advances in vector-mediated antibody expression have demonstrated the potential for such interventions to prevent infection and treat disease. As such, it offers an alternative to immunogen-based vaccine design and a novel therapeutic intervention by enabling precise manipulation of humoral immunity. Success translating these approaches to patients may enable the development of effective prevention against previously intractable pathogens that evade immunity such as HIV, influenza, malaria or HCV and may also enable new treatment options for neurodegenerative diseases such as Alzheimer’s disease.

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“…169,170 This approach made use of adeno-associated viralmediated transfer of genes encoding full anti-nicotine and anticocaine mAb, and showed efficacy in various pre-clinical models. 169,170 Gene transfer strategies have also been examined to prolong, or enhance, the effect of cocaine hydrolases.…”

Section: Gene Therapymentioning

confidence: 99%

Biologics to treat substance use disorders: Current status and new directions

Pravetoni

2016

Human Vaccines & Immunotherapeutics

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AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

Cited by 42 publications

References 53 publications

Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody

Recombinant AAV-mediated in vivo long-term expression and antitumour activity of an anti-ganglioside GM3(Neu5Gc) antibody

Engineering humoral immunity as prophylaxis or therapy

Biologics to treat substance use disorders: Current status and new directions

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