The goal of this combination Phase I / Phase II STTR project is to test the hypothesis that anti-drug monoclonal antibodies are a safe and effective therapy for the medical problems associated with phencyclidine (PCP) abuse. There are currently no specific medications for treating the medical problems caused by acute or chronic PCP abuse. Thus, long-lasting medications that could prevent or minimize PCP effects, and the need for day-to-day patient compliance are sorely needed. We hypothesize that antibody-based medications (developed and produced in Phase I of this STTR), with their extremely favorable pharmacokinetic properties and unique mechanisms of action might provide new hope as an innovative and novel medication for treating PCP abuse. The medication designed for this project is a chimeric monoclonal antibody produced in plants, which was engineered from the antigen binding variable regions of an anti-PCP mouse monoclonal antibody and the constant regions of a human IgG2 antibody. This new medication, called ch-mAb6B5, will have a combination of the proven effectiveness of the mouse anti-PCP monoclonal antibody combined with the safety of a human monoclonal antibody. The Phase I application of this STTR focuses on the expression of this antibody in a recombinant, plant based expression and manufacturing system using tobacco plants. This system has already successfully delivered products to the clinic for human testing and a strong commercialized manufacturing system already exists. By using this new paradigm in expression and manufacturing, the goal of this STTR is to provide safe, efficacious and cost effective therapies for drug abuse treatment. This combined expression, manufacturing and clinical effort is needed to confirm the utility of this approach. The potential for long term impact on health care due to increase in drug abuse could be very large and will be a public burden. Very few therapies are available in this area and these types of industry/academic consortia are necessary to bring these treatments forward. The goal of this Phase II STTR project is to test the hypothesis that anti-drug monoclonal antibodies are a safe and effective therapy for the medical problems associated with phencyclidine (PCP) abuse. There are currently no specific medications for treating the medical problems caused by acute or chronic PCP abuse. Thus, long-lasting medications that could prevent or minimize PCP effects, and the need for day-to-day patient compliance are sorely needed. We hypothesize that antibody-based medications (developed and produced in Phase I of this STTR), with their extremely favorable pharmacokinetic properties and unique mechanisms of action might provide new hope as an innovative and novel medication for treating PCP abuse. The medication designed for this project is a chimeric monoclonal antibody produced in plants, which was engineered from the antigen binding variable regions of an anti-PCP mouse monoclonal antibody and the constant regions of a human IgG2 antibody. This new medication, called ch-mAb6B5, will have a combination of the proven effectiveness of the mouse anti-PCP monoclonal antibody combined with the safety of a human monoclonal antibody. During this Phase II STTR project, ch-mAb6B5 will be tested in human clinical trials to determine if it is safe and effective in the treatment of PCP abuse. In these studies, safety and pharmacokinetic measurements in volunteer human PCP abusers will be used to determine the safety profile, dosing strategy, and biological dose of ch-mAb6B5. The efficacy and duration of action of chmAb6B5 will then be determined in a similar group of patients undergoing outpatient cognitive-behavioral therapy for their PCP abuse. The objective knowledge gained from these Phase I and II clinical trials will be used to determine safety of the medications and the clinical scenarios (e.g., chronic PCP abuse) in which the medications could be efficacious and beneficial.
