PMID- 7910405
OWN - NLM
STAT- MEDLINE
DCOM- 19940616
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 91
IP  - 10
DP  - 1994 May 10
TI  - Cytotoxic T lymphocytes with a grafted recognition specificity for 
      ERBB2-expressing tumor cells.
PG  - 4318-22
AB  - Experimental approaches which exploit the targeted cytolytic activity of 
      lymphocytes are being developed for cancer therapy. We generated cytotoxic T 
      lymphocytes (CTLs) with specificity for ERBB2 receptor-expressing tumor cells. A 
      binding function was conferred directly on the zeta chain of the T-cell receptor 
      (TCR) complex to circumvent major histocompatibility complex-restricted antigen 
      recognition through the alpha and beta chains of the TCR. A chimeric gene was 
      constructed which encoded a single-chain Fv antibody (scFv, consisting of the 
      joined heavy- and light-chain variable domains of a monoclonal antibody against 
      the extracellular domain of the ERBB2 receptor), a hinge region as a spacer, and 
      the zeta chain of the TCR. This gene was introduced into CTLs by retroviral gene 
      transfer. The signaling potential of the scFv/hinge/zeta receptors was 
      demonstrated by secretion of interferon gamma upon coincubation with 
      ERBB2-expressing cells. Target cells expressing the ERBB2 gene were lysed in 
      vitro with high specificity by the scFv/hinge/zeta-expressing T cells. The growth 
      of ERBB2-transformed cells in athymic nude mice was retarded by adoptively 
      transferred scFv/hinge/zeta-expressing CTLs. Transduced CTLs labeled with a 
      fluorescent dye were specifically detected in tumor sections. Our results suggest 
      that tumor cell lysis by CTLs grafted in vitro with a major histocompatibility 
      complex-independent recognition could become a gene-therapy approach to cancer 
      treatment.
FAU - Moritz, D
AU  - Moritz D
AD  - Friedrich Miescher-Institute, Basel, Switzerland.
FAU - Wels, W
AU  - Wels W
FAU - Mattern, J
AU  - Mattern J
FAU - Groner, B
AU  - Groner B
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Biomarkers, Tumor
MH  - Cell Line
MH  - Cloning, Molecular
MH  - *Cytotoxicity, Immunologic
MH  - Enzyme-Linked Immunosorbent Assay
MH  - ErbB Receptors/biosynthesis/*immunology/isolation & purification
MH  - Humans
MH  - Interferon-gamma/*biosynthesis
MH  - Major Histocompatibility Complex
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Nude
MH  - Proto-Oncogene Proteins/biosynthesis/*immunology/isolation & purification
MH  - Receptor, ErbB-2
MH  - Receptors, Antigen, T-Cell/biosynthesis/immunology/isolation & purification
MH  - Recombinant Fusion Proteins/biosynthesis/immunology/isolation & purification
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology/*metabolism
MH  - Transfection
PMC - PMC43776
EDAT- 1994/05/10 00:00
MHDA- 1994/05/10 00:01
PMCR- 1994/11/10
CRDT- 1994/05/10 00:00
PHST- 1994/05/10 00:00 [pubmed]
PHST- 1994/05/10 00:01 [medline]
PHST- 1994/05/10 00:00 [entrez]
PHST- 1994/11/10 00:00 [pmc-release]
AID - 10.1073/pnas.91.10.4318 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1994 May 10;91(10):4318-22. doi: 
      10.1073/pnas.91.10.4318.