Targeting TARP, a novel breast and prostate tumor-associated antigen, with T cell receptor-like human recombinant antibodies

Malka Epel, Irit Carmi, Sharon Soueid-Baumgarten, Sang Kon Oh, Tapan Bera, Ira Pastan, Jay Berzofsky, Yoram Reiter

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

MHC class I molecules are important components of immune surveillance. There are no available methods to directly visualize and determine the quantity and distribution of MHC/peptide complexes on individual cells or to detect such complexes on antigen-presenting cells in tissues. MHC-restricted relcombinant antibodies with the same specificity of T cell receptors (TCR) may become a valuable tool to address these questions. They may also serve as valuable targeting molecules that mimic the specificity of cytotoxic T cells. We isolated by phage display a panel of human recombinant Fab antibodies with peptide-specific, MHC-restricted TCR-like reactivity directed toward HLA-A2-restricted T cell epitopes derived from a novel antigen termed TCRγ alternative reading frame protein (TARP) which is expressed on prostate and breast cancer cells. We have characterized one of these recombinant antibodies and demonstrated its capacity to directly detect specific HLA-A2/TARP T cell epitopes on antigen-presenting cells that have complexes formed by naturally occurring active intracellular processing of the antigen, as well as on the surface of tumor cells. Moreover, by genetic fusion we armed the TCR-like antibody with a potent toxin and demonstrated that it can serve as targeting moiety killing tumor cells in a peptide-specific, MHC-restricted manner similar to cytotoxic T lymphocytes.

Original languageEnglish (US)
Pages (from-to)1706-1720
Number of pages15
JournalEuropean Journal of Immunology
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Immunotoxin
  • MHC
  • Recombinant antibody
  • T-cell receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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