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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.
- Source :
-
Neoplasia . Jun/Jul99, Vol. 1 Issue 2, p123. 5p. - Publication Year :
- 1999
-
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 CD8+ T lymphocyte functions can be synergistically targeted against tumor cells. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENE therapy
*PROSTATE cancer
*IMMUNOTHERAPY
*GENETIC transformation
Subjects
Details
- Language :
- English
- ISSN :
- 15228002
- Volume :
- 1
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Neoplasia
- Publication Type :
- Academic Journal
- Accession number :
- 8947660
- Full Text :
- https://doi.org/10.1038/sj.neo.7900018