Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor γ chain

P. Hwu, G. E. Shafer, J. Treisman, D. G. Schindler, G. Gross, R. Cowherd, S. A. Rosenberg, Z. Eshhar

Research output: Contribution to journalArticlepeer-review

Abstract

To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the γ subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.

Original languageEnglish (US)
Pages (from-to)361-366
Number of pages6
JournalJournal of Experimental Medicine
Volume178
Issue number1
DOIs
StatePublished - Jul 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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