Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors

J Immunol. 1993 Dec 1;151(11):6577-82.

Abstract

Cell surface molecules essential for the transformed phenotype or growth of malignant cells are attractive targets for anticancer immunotherapy. Antibodies specific to Neu/HER2, a human adenocarcinoma-associated growth factor receptor, were demonstrated to have tumor-inhibitory capacity. Yet, the inefficient accessibility of antibodies to solid tumors limits their clinical use. To redirect effector lymphocytes to adenocarcinomas, we constructed and functionally expressed in T cells chimeric single chain receptor genes incorporating both the Ag-binding domain of anti-Neu/HER2 antibodies and the zeta-signal-transducing subunit of the TCR/CD3 complex or the gamma-signal-transducing subunit of the Ig Fc receptor complex. Surface expression of the anti-Neu/HER2 chimeric genes in cytotoxic T cell hybridomas endowed them with specific Neu/HER2 recognition enabling their activation for IL-2 production and lysis of transformed cells overexpressing Neu/HER2. These chimeric genes hold promise for the immunotherapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics*
  • Cytotoxicity, Immunologic
  • ErbB Receptors / immunology*
  • Membrane Proteins / genetics*
  • Mice
  • Proto-Oncogene Proteins / immunology*
  • Receptor, ErbB-2
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Fc / genetics*
  • Recombinant Fusion Proteins / genetics*
  • T-Lymphocytes / immunology*
  • Transfection

Substances

  • Antibodies, Monoclonal
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • antigen T cell receptor, zeta chain
  • ErbB Receptors
  • Receptor, ErbB-2