PMID- 8593604
OWN - NLM
STAT- MEDLINE
DCOM- 19960410
LR  - 20201226
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 2
IP  - 8
DP  - 1995 Oct
TI  - A spacer region between the single chain antibody- and the CD3 zeta-chain domain 
      of chimeric T cell receptor components is required for efficient ligand binding 
      and signaling activity.
PG  - 539-46
AB  - The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) could become the 
      basis of a biological cancer therapy. The recognition specificity of cytotoxic T 
      lymphocytes (CTLs) can be genetically modified by stable introduction of chimeric 
      T cell receptor genes and thus be directed towards tumor cells. We designed a 
      recombinant T cell receptor (TCR) component consisting of a single chain Fv 
      derivative of a monoclonal antibody (scFv) serving as the extracellular 
      antigen-binding domain and the zeta-chain of the TCR/CD3 complex serving as a 
      signal transducing domain. Three chimeric receptor constructs differing in their 
      molecular structure were derived and their functions in transduced T cells 
      compared. A construct in which the scFv domain, specific for the ErbB-2 receptor, 
      was fused directly to the zeta-chain, and two constructs containing different 
      hinge regions between the functional domains, were made. The hinge regions serve 
      as spacers which increase the distance of the scFv moiety from the plasma 
      membrane. Only the two scFv-zeta chimeras containing a hinge region showed ErbB-2 
      binding activity, when expressed in T cells. The scFv-zeta construct which lacks 
      a spacer segment did not. Consistently, only the spacer-containing chimeras 
      transduced T cell receptor signals following ErbB-2 mediated crosslinking. An 
      increase in intracellular Ca2+ concentrations and cytokine secretion was 
      observed. ErbB-2 expressing tumor cells were efficiently lysed by CTLs which 
      expressed the spacer-containing scFv-zeta chimeras. Our results will help to 
      optimize the design of recombinant T cell receptor components useful in the 
      grafting of a specificity of recognition on to cytotoxic T cells and possibly the 
      gene therapy of cancer.
FAU - Moritz, D
AU  - Moritz D
AD  - Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, 
      Germany.
FAU - Groner, B
AU  - Groner B
LA  - eng
PT  - Journal Article
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (DNA Primers)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (antigen T cell receptor, zeta chain)
RN  - 82115-62-6 (Interferon-gamma)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cytotoxicity, Immunologic
MH  - DNA Primers
MH  - Genetic Therapy
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Leukemia, T-Cell
MH  - Lymphocyte Depletion
MH  - Membrane Proteins/*biosynthesis/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Receptors, Antigen, T-Cell/*biosynthesis/*genetics/physiology
MH  - Recombinant Fusion Proteins/biosynthesis/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tumor Cells, Cultured
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
PST - ppublish
SO  - Gene Ther. 1995 Oct;2(8):539-46.