PMID- 15664164
OWN - NLM
STAT- MEDLINE
DCOM- 20050307
LR  - 20210102
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 22
IP  - 1
DP  - 2005 Jan
TI  - Cooperation of human tumor-reactive CD4+ and CD8+ T cells after redirection of 
      their specificity by a high-affinity p53A2.1-specific TCR.
PG  - 117-29
AB  - Efficient immune attack of malignant disease requires the concerted action of 
      both CD8+ CTL and CD4+ Th cells. We used human leukocyte antigen (HLA)-A*0201 
      (A2.1) transgenic mice, in which the mouse CD8 molecule cannot efficiently 
      interact with the alpha3 domain of A2.1, to generate a high-affinity, 
      CD8-independent T cell receptor (TCR) specific for a commonly expressed, 
      tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the human p53 
      tumor suppressor protein. Retroviral expression of this CD8-independent, 
      p53-specific TCR into human T cells imparted the CD8+ T lymphocytes with broad 
      tumor-specific CTL activity and turned CD4+ T cells into potent tumor-reactive, 
      p53A2.1-specific Th cells. Both T cell subsets were cooperative and interacted 
      synergistically with dendritic cell intermediates and tumor targets. The 
      intentional redirection of both CD4+ Th cells and CD8+ CTL by the same 
      high-affinity, CD8-independent, tumor-specific TCR could provide the basis for 
      novel broad-spectrum cancer immunotherapeutics.
FAU - Kuball, Jurgen
AU  - Kuball J
AD  - Department of Hematology and Oncology, Johannes Gutenberg University, 55101 
      Mainz, Germany.
FAU - Schmitz, Frank W
AU  - Schmitz FW
FAU - Voss, Ralf-Holger
AU  - Voss RH
FAU - Ferreira, Edite Antunes
AU  - Ferreira EA
FAU - Engel, Renate
AU  - Engel R
FAU - Guillaume, Philippe
AU  - Guillaume P
FAU - Strand, Susanne
AU  - Strand S
FAU - Romero, Pedro
AU  - Romero P
FAU - Huber, Christoph
AU  - Huber C
FAU - Sherman, Linda A
AU  - Sherman LA
FAU - Theobald, Matthias
AU  - Theobald M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cloning, Molecular
MH  - Flow Cytometry
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell/genetics/immunology/*metabolism
MH  - *T-Cell Antigen Receptor Specificity
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transduction, Genetic
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/genetics/immunology/metabolism
EDAT- 2005/01/25 09:00
MHDA- 2005/03/08 09:00
CRDT- 2005/01/25 09:00
PHST- 2004/06/22 00:00 [received]
PHST- 2004/11/10 00:00 [revised]
PHST- 2004/12/01 00:00 [accepted]
PHST- 2005/01/25 09:00 [pubmed]
PHST- 2005/03/08 09:00 [medline]
PHST- 2005/01/25 09:00 [entrez]
AID - S1074-7613(04)00382-6 [pii]
AID - 10.1016/j.immuni.2004.12.005 [doi]
PST - ppublish
SO  - Immunity. 2005 Jan;22(1):117-29. doi: 10.1016/j.immuni.2004.12.005.