Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Academic Article uri icon

Overview

abstract

  • Artificial receptors provide a promising approach to target T lymphocytes to tumor antigens. However, the receptors described thus far produce either an activation or a co-stimulatory signal alone, thus limiting the spectrum of functions accomplished by the genetically modified cells. Here we show that human primary T lymphocytes expressing fusion receptors directed to prostate-specific membrane antigen (PSMA) and containing combined T-cell receptor-zeta (TCRzeta), and CD28 signaling elements, effectively lyse tumor cells expressing PSMA. When stimulated by cell-surface PSMA, retrovirally transduced lymphocytes undergo robust proliferation, expanding by more than 2 logs in three weeks, and produce large amounts of interleukin-2 (IL-2). Importantly, the amplified cell populations retain their antigen-specific cytolytic activity. These data demonstrate that fusion receptors containing both TCR and CD28 signaling moieties are potent molecules able to redirect and amplify human T-cell responses. These findings have important implications for adoptive immunotherapy of cancer, especially in the context of tumor cells that fail to express major histocompatibility complex antigens and co-stimulatory molecules.

publication date

  • January 1, 2002

Research

keywords

  • CD28 Antigens
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • T-Lymphocytes, Cytotoxic

Identity

Scopus Document Identifier

  • 0036137615

Digital Object Identifier (DOI)

  • 10.1038/nbt0102-70

PubMed ID

  • 11753365

Additional Document Info

volume

  • 20

issue

  • 1