PMID- 15871677
OWN - NLM
STAT- MEDLINE
DCOM- 20050823
LR  - 20231213
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 16
IP  - 4
DP  - 2005 Apr
TI  - Transfer of a TCR gene derived from a patient with a marked antitumor response 
      conveys highly active T-cell effector functions.
PG  - 457-72
AB  - The genes for the alpha and beta chains of a highly reactive anti-MART-1 T-cell 
      receptor were isolated from T-lymphocytes that mediated in vivo regression of 
      tumor in a patient with metastatic melanoma. These genes were cloned and inserted 
      into MSCV-based retroviral vectors. After transduction, greater than 50% gene 
      transfer efficiency was demonstrated in primary T-lymphocytes stimulated by an 
      anti-CD3 antibody. The specificity and biologic activity of TCR gene-transduced 
      T-cells was determined by cytokine production after coculture of T-cells with 
      stimulator cells pulsed with MART-1 peptide. The production of interferon-gamma 
      and granulocyte macrophage-colony stimulating factor (GM-CSF) was comparable to 
      highly active MART-1 specific peripheral blood lymphocytes (PBL) in the amount of 
      cytokine produced and transduced cells recognized peptide pulsed cells at 
      dilutions similar to cytotoxic T lymphocyte (CTL) clones. Human leukocyte antigen 
      (HLA) class I restricted recognition was demonstrated by mobilization of 
      degranulation marker CD107a, by cell lysis, by cytokine production, and by 
      proliferation in the presence of HLA-A2-positive but not HLA-A2-negative melanoma 
      cell lines. Similar data was obtained when tumor-infiltrating lymphocytes (TIL) 
      were transduced with the TCR genes, converting previously nonreactive cells to 
      tumor reactive cells. TCR-transduced T-cells are thus attractive candidates for 
      evaluation in cell transfer therapies of patients with cancer.
FAU - Hughes, Marybeth S
AU  - Hughes MS
AD  - Surgery Branch, National Cancer Institute, National Institutes of Health, 
      Bethesda, MD 20892, USA.
FAU - Yu, Yik Y L
AU  - Yu YY
FAU - Dudley, Mark E
AU  - Dudley ME
FAU - Zheng, Zhili
AU  - Zheng Z
FAU - Robbins, Paul F
AU  - Robbins PF
FAU - Li, Yong
AU  - Li Y
FAU - Wunderlich, John
AU  - Wunderlich J
FAU - Hawley, Robert G
AU  - Hawley RG
FAU - Moayeri, Morvarid
AU  - Moayeri M
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
FAU - Morgan, Richard A
AU  - Morgan RA
LA  - eng
GR  - Z01 SC003811-31/SC/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cytokines)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Lysosomal-Associated Membrane Protein 1)
RN  - 0 (Lysosomal Membrane Proteins)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Antigens, CD/immunology/metabolism
MH  - Antigens, Neoplasm
MH  - Cell Proliferation
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Gene Transfer Techniques
MH  - Genes, T-Cell Receptor/*genetics/immunology
MH  - Genetic Vectors/genetics/immunology
MH  - HLA-A2 Antigen/immunology/metabolism
MH  - Humans
MH  - Immunotherapy/methods
MH  - Leukemia, T-Cell/genetics/immunology
MH  - Lysosomal-Associated Membrane Protein 1
MH  - Lysosomal Membrane Proteins
MH  - MART-1 Antigen
MH  - Melanoma/immunology/pathology/*therapy
MH  - Neoplasm Proteins/immunology
MH  - T-Lymphocytes/*immunology
MH  - Transduction, Genetic
MH  - Tumor Cells, Cultured
PMC - PMC1476695
MID - NIHMS10165
EDAT- 2005/05/06 09:00
MHDA- 2005/08/24 09:00
PMCR- 2008/01/27
CRDT- 2005/05/06 09:00
PHST- 2005/05/06 09:00 [pubmed]
PHST- 2005/08/24 09:00 [medline]
PHST- 2005/05/06 09:00 [entrez]
PHST- 2008/01/27 00:00 [pmc-release]
AID - 10.1089/hum.2005.16.457 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2005 Apr;16(4):457-72. doi: 10.1089/hum.2005.16.457.