IgAim: cell surface Ig-aimed immune memory erasers for the therapy of autoimmune diseases and B leukemia.

Autoimmune diseases are caused by the misdirection of the immune system as the side effect of antibody diversity, wherein each B cell possesses unique characteristics defined by its antibodies. To address this issue, I have developed several cell surface immunoglobulin (Ig)-aimed immune memory erasers (IgAim) that consist of toxins explicitly targeted to cell surface Ig (sIg) on B cells. IgAim is created by replacing the receptor binding domain of diphtheria toxin with Staphylococcal protein A (SpA), affibodies, or specific antigens. The toxins IgAimG and IgAimA selectively killed sIgG+ and sIgA+ B cells, respectively. Treatment with these proteins kills between 90% and 99% of the target cell population without displaying toxicity toward other classes of B cells or nontarget cell types. The specificity of IgAim is highlighted by IgAimP7 which exclusively kills B cells expressing an antibody against pollen allergen Phleum pratense (Phl) p7. IgAim could be the basis of an effective future family of therapeutic agents for treating autoimmune diseases as well as B leukemia.