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Arming T cells with activating FcγRIIIa receptors for antibody redirected lysis of cancer cells

      Background: Adoptive T cell therapy (ACT) has proven to be efficient against hematologic malignancies. As ACT is mostly based on artificial receptors recognizing single antigens expressed on cancer cells, major limitations include antigen-loss of tumor cells as well as side effects. Designing T cells with variable antigen targeting limited in time would have considerable advantages both in terms of safety and efficacy. In order to create such a flexible but efficient system, we armed T cells with fusion receptors consisting of the extracellular portion of an antibody-binding-receptor (Fcγ receptor IIIA, synonymous CD16) and the intracellular domains of CD28 and CD3z. Combining this platform with different clinically approved monospecific antibodies could provide a versatile treatment strategy. Variation of the specificity of the antibody and the receptor affinity for its Fc part could potentially enhance efficacy and safety of either therapy alone.
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