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

Prostate. 2004 Sep 15;61(1):12-25. doi: 10.1002/pros.20073.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antigens, Surface / immunology*
  • Cell Line, Tumor
  • Cloning, Molecular
  • Cytotoxicity Tests, Immunologic
  • Flow Cytometry
  • Glutamate Carboxypeptidase II / immunology*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology*
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light Chains / immunology
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Precipitin Tests
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology*


  • Antibodies, Monoclonal
  • Antigens, Surface
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II