Antigen-directed therapies for autoantibody associated neuroinflammatory diseases.

In this COMBINE proposal the team seeks to develop an approach to facilitate the discovery of autoantibodies directed to cell surface antigens that may be directly pathogenic. The specificity of these new autoantibodies will be deeply characterized and recombinant human monoclonal antibodies (mAbs) will be generated by single-cell sequencing. These recombinant mAbs will allow the development of animal models of disease. Tools to treat these new models in an antigen-specific manner will be pursued using novel approaches to identify neutralizing antibodies to target antibodies directly and by developing CAAR-T cells, T cell-engagers (TCE), and NK-cell Engagers (NKCEs) to target the autoantibody-producing B-cells. The proposal describes the methodologies we’ve developed to pursue this goal and how we will develop new approaches. We also describe as proof of principle a new autoantibody-dependent neuroinflammatory syndrome that will be the first target for this integrated approach.