Development and applications of surface-linked single chain antibodies against T-cell antigens

Matthew D. Griffin, Philmore O. Holman, Qizhi Tang, Neda Ashourian, Ulf Korthäuer, David M. Kranz, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

Abstract

In this report the use of surface-linkage to expand the potential experimental and therapeutic applications of single chain antibody (scFv) constructs is reviewed. A strategy for the generation and functional characterization of surface-linked scFvs that bind selectively to the T-cell proteins CD3ε, CD28, and CD152 (CTLA-4) is described in detail. Experimental examples are provided of the use of these constructs to study the positive and negative regulation of T-cell activation and to manipulate the in vivo immunogenicity of tumor cells. In addition, a novel system for Simultaneous T-cell Activation and Retroviral Transduction (START) is described in which retroviral packaging cells are rendered mitogenic for T lymphocytes by combined expression of surface-linked scFvs. Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated.

Original languageEnglish (US)
Pages (from-to)77-90
Number of pages14
JournalJournal of Immunological Methods
Volume248
Issue number1-2
DOIs
StatePublished - Feb 1 2001

Keywords

  • CD152
  • CD28
  • CD3
  • Co-stimulation
  • Immunological tolerance
  • Immunomodulation
  • Monoclonal antibodies
  • Neoplasia
  • Protein engineering
  • Retroviral gene transfer
  • T-cell
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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