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. Academic Article uri icon

Overview

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 zeta 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.

publication date

  • June 1, 1999

Research

keywords

  • Antigens, Surface
  • Carboxypeptidases
  • Cytokines
  • Gene Transfer Techniques
  • Prostatic Neoplasms
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC1508130

Scopus Document Identifier

  • 0033139686

Digital Object Identifier (DOI)

  • 10.1038/sj.neo.7900018

PubMed ID

  • 10933046

Additional Document Info

volume

  • 1

issue

  • 2