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 ζ 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:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033139686&partnerID=40&md5=f4e29c26c2bc04d67d5a7b680e8d948b
Notes:	Article -- Export Date: 16 August 2016 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/96506