Combining Active Immunization with Monoclonal Antibody Therapy To Facilitate Early Initiation of a Long-Acting Anti-Methamphetamine Antibody Response

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• 作者：Michael D. Hambuchen ; F. Ivy Carroll ; Daniela R眉edi-Bettschen ; Howard P. Hendrickson ; Leah J. Hennings ; Bruce E. Blough ; Lawrence E. Brieaddy ; Ramakrishna R. Pidaparthi ; S. Michael Owens
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：June 11, 2015
• 年：2015
• 卷：58
• 期：11
• 页码：4665-4677
• 全文大小：526K
• ISSN：1520-4804

文摘

We hypothesized that an anti-METH mAb could be used in combination with a METH-conjugate vaccine (MCV) to safely improve the overall quality and magnitude of the anti-METH immune response. The benefits would include immediate onset of action (from the mAb), timely increases in the immune responses (from the combined therapy) and duration of antibody response that could last for months (from the MCV). A novel METH-like hapten (METH-SSOO9) was synthesized and then conjugated to immunocyanin monomers of keyhole limpet hemocyanin (IC_KLH) to create the MCV IC_KLH-SOO9. The vaccine, in combination with previously discovered anti-METH mAb7F9, was then tested in rats for safety and potential efficacy. The combination antibody therapy allowed safe achievement of an early high anti-METH antibody response, which persisted throughout the study. Indeed, even after 4 months the METH vaccine antibodies still had the capacity to significantly reduce METH brain concentrations resulting from a 0.56 mg/kg METH dose.