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Prostate. 2004 Sep 15;61(1):12-25.

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

Author information

1
Biotherapeutics Development Lab, Division of Hematology-Oncology, Beth Israel Deaconess Medical Center and Harvard Institute of Human Genetics, Harvard Medical School, Boston, Massachusetts, USA.

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.

PMID:
15287090
DOI:
10.1002/pros.20073
[Indexed for MEDLINE]

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