MONOCLONAL ANTIBODIES FOR ALZHEIMER'S IMMUNOTHERAPY

DESCRIPTION (PROVIDED BY APPLICANT): Transgenic mice administered anti-amyloid peptide antibodies, acutely or subchronically, show markedly improved learning and memory performance. Recent reports suggest that the toxicity of the amyloid peptide and other amyloidogenic proteins lies not in the insoluble fibrils that accumulate but rather in the soluble oligomeric intermediates. A panel of monclonal antibodies has been developed by Mapp Biopharmaceutical, which recognizes the internal domain of soluble amyloid beta peptide. These antibodies are candidates for use in passive immunotherapy. The potential advantages of a passive approach include: (1) the dose of drug given to any patient can be determined precisely, eliminating potential variability which will occur with active immunization; (2) therapy can be started or stopped at any time. Potential disadvantages include: (1) whether enough reagent can be generated to treat large numbers of individuals and (2) cost. The purpose of this study is to evaluate a set of candidate monoclonal antibodies that are intended to contribute to our overall understanding of the benefits of passive Alzheimer's immunization in humans and produce these antibodies in a system, which ultimately minimizes the capital burden of antibody drug production and hence reduces the overall costs. In Specific Aim 1, the panel will be characterized with respect to affinity, oligomer binding, and epitope specificity. The variable regions of a selection of monoclonals will then be cloned in Specific Aim 2 and the genes introduced the into plant expression vectors as both mouse IgG and mouse-human chimeric IgG. Finally, in Specific Aim 3, the expression vectors will be introduced into plants to generate quantities of monoclonal sufficient for in vitro comparison to the original hybridoma expressed monoclonal.