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Immunotoxins can kill cancer cells while allowing healthy, essential cells to survive. As a result, patients receiving an immunotoxin are less likely to experience the deleterious side-effects associated with non-discriminate therapies such as chemotherapy or radiation therapy. Unfortunately, the continued administration of immunotoxins often leads to a reduced patient response due to the formation of neutralizing antibodies against immunogenic B-cell and T-cell epitopes contained within PE. To improve the therapeutic effectiveness of PE-containing immunotoxins through multiple rounds of drug administration, NIH inventors have sought to remove the B-cell and T-cell epitopes within PE. Previous work demonstrated that the removal of the major B-cell epitopes from PE reduced the immunogenicity of PE. This technology involves the identification of major T-cell epitopes on PE, and the removal of the primary T-cell epitope by mutation or deletion. By combining the T-cell epitope mutations with modifications that remove B-cell epitopes, it is possible to create PE-based immunotoxins that have even greater resistance to the formation of neutralizing antibodies. Immunotoxins containing these new PE-variants are expected to have improved therapeutic efficacy.
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An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...