Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen Journal Article


Authors: Gong, M. C.; Latouche, J. B.; Krause, A.; Heston, W. D. W.; Bander, N. H.; Sadelain, M.
Article Title: Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen
Abstract: The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ΞΆ chain fusion receptor specific for prostate-specific membrane antigen (PSMA) termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CDS+ T lymphocyte functions can be synergistically targeted against tumor cells.
Keywords: signal transduction; aged; aged, 80 and over; middle aged; flow cytometry; t lymphocyte; t-lymphocytes; mouse; animal; metabolism; animals; mice; gene transfer; prostate cancer; prostatic neoplasms; membrane antigen; cytokine; biosynthesis; immunology; cytokines; hybrid protein; immunotherapy; recombinant fusion proteins; prostate tumor; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; gene therapy; fibroblast; fibroblasts; epithelium cell; epithelial cells; cell separation; cell strain 3t3; cd28 antigen; antigens, cd28; retrovirus; retroviridae; glutamate carboxypeptidase ii; glutamate carboxypeptidase ii, human; antigens, surface; 3t3 cells; gene transfer techniques; carboxypeptidase; coculture; coculture techniques; costimulation; humans; human; male; article; carboxypeptidases; retroviral-mediated gene transfer
Journal Title: NeoPlasia
Volume: 1
Issue: 2
ISSN: 1522-8002
Publisher: Elsevier Science Inc.  
Date Published: 1999-06-01
Start Page: 123
End Page: 127
Language: English
PUBMED: 10933046
PROVIDER: scopus
PMCID: PMC1508130
DOI: 10.1038/sj.neo.7900018
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Warren Heston
    89 Heston
  2. Michel W J Sadelain
    453 Sadelain
  3. Michael Gong
    8 Gong
  4. Anja   Krause
    6 Krause