Anti‐prostate specific membrane antigen designer T cells for prostate cancer therapy

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Abstract
Background: Designer T cells are T lymphocytes engineered toward specific antibody‐type membrane antigens through chimeric immunoglobulin‐T‐cell receptor (IgTCR) genes that have been used for adoptive cellular immunotherapy. We have extended this approach to prostate specific membrane antigen (PSMA) as a means to attack prostate cancer.Methods: A chimeric anti‐PSMA IgTCR gene was constructed based on an anti‐PSMA monoclonal antibody, 3D8. Both T‐cell lines and primary cultured human T lymphocytes were transduced with the chimeric anti‐PSMA IgTCR construct and were analyzed for IgTCR expression, specific activation by PSMA, cytotoxicity against PSMA‐expressing tumor cells in vitro, and retardation of tumor growth in an animal model.Results: The IgTCR was incorporated into the TCR–CD3 complex and formed a functional chimeric complex. The IgTCR‐modified T cells were specifically activated through the chimeric receptor with PSMA as measured by IL‐2 production and increased CD25 expression and specifically lysed the PSMA‐expressing prostate cancer cells in vitro as well as retarded tumor growth in an animal model.Conclusions: The anti‐PSMA designer T cells exhibit an antibody‐type specificity that can recognize PSMA expressing tumor cells in a MHC‐independent fashion, resulting in T‐cell activation, target cell lysis in vitro and inhibition of tumor growth in vivo.