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Redirecting effector T cells through their IL-2 receptors

Academic Article
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Overview

authors

  • Lustgarten, J.
  • Marks, J.
  • Sherman, Linda

publication date

  • January 1999

journal

  • Journal of Immunology  Journal

abstract

  • Fusion proteins constructed of a tumor-specific Ab joined to IL-2 (Ab-IL-2) have been used in the past to deliver cytokine directly to the site of tumor cells in vivo. These molecules mimic the activity of IL-2 and assist in activating and expanding antitumor effector cells. To enhance the cytolytic activity of CTL specific for peptide epitopes of the Her-2/neu tumor Ag presented by HLA-A*0201 molecules, a fusion protein was constructed consisting of a single chain Ab specific for Her-2/neu, linked to IL-2 (neu-Ab-IL-2). When added to a mixture of tumor cells and Her-2/neu-specific CTL, the protein was found to augment lysis of tumor cells. In addition, the hybrid molecule also promoted lysis of Her-2/neu expressing tumors by non-tumor-specific cloned T cell lines, including Th1 CD4 cells. Analysis of the mechanism of cytotoxicity revealed that the fusion protein mediates the formation of stable conjugates between T cells expressing IL-2R and tumor cells expressing Her-2/neu, resulting in lysis through the Fas-Fas ligand pathway. Lysis induction was independent of specific engagement by the TCR. When tested for its ability to enhance tumor cell eradication by Her-2/neu-specific CD8+ T cells in an adoptive transfer model in SCID mice, neu-Ab-IL-2 facilitated the elimination of tumor cells in vivo. Surprisingly, the combination of non-tumor-specific CD8+ T cells and fusion protein also induced a significant delay of tumor growth. This represents a novel approach for redirecting non-tumor-specific T cells to eliminate tumors.

subject areas

  • Adoptive Transfer
  • Animals
  • Antineoplastic Agents
  • Cell Line
  • Cytotoxicity, Immunologic
  • Female
  • Growth Inhibitors
  • Humans
  • Immunoglobulin Fragments
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Receptor, ErbB-2
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 9886407
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Additional Document Info

start page

  • 359

end page

  • 365

volume

  • 162

issue

  • 1

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