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    James Torchia.
    B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor, otherwise known as idiotype. The tumor idiotype differs from patient to patient, however, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype using a semi-synthetic personalized therapeutic that is more practical to produce on a patient-by-patient basis than monoclonal antibodies. In this method, a small peptide with affinity for a tumor idiotype is identified by screening a library, chemically synthesized, and then affixed to the amino-terminus of a pre-made IgG Fc protein. We demonstrate that the resultant semi-synthetic anti-idiotype peptibodies kill tumor cells in vitro with specificity, trigger tumor cell phagocytosis by macrophages, and efficiently clear human lymphoma in a murine xenograft model. Our results suggest that this method could be used to target tumor with true precision on a personalized basis.
    Digital Access   2015