PMID- 16540688
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20211020
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 6
DP  - 2006 Mar 15
TI  - Alphabeta T-cell receptor engineered gammadelta T cells mediate effective 
      antileukemic reactivity.
PG  - 3331-7
AB  - Retroviral transfer of T-cell receptors (TCR) to peripheral blood-derived T cells 
      generates large numbers of T cells with the same antigen specificity, potentially 
      useful for adoptive immunotherapy. One drawback of this procedure is the 
      formation of mixed TCR dimers with unknown specificities due to pairing of 
      endogenous and introduced TCR chains. We investigated whether gammadelta T cells 
      can be an alternative effector population for TCR gene transfer because the 
      gammadeltaTCR is not able to form dimers with the alphabetaTCR. Peripheral 
      blood-derived gammadelta T cells were transduced with human leukocyte antigen 
      (HLA) class I- or HLA class II-restricted minor histocompatibility antigen (mHag) 
      or virus-specific TCRs. Because most gammadelta T cells do not express CD4 and 
      CD8, we subsequently transferred these coreceptors. The TCR-transduced gammadelta 
      T cells exerted high levels of antigen-specific cytotoxicity and produced 
      IFN-gamma and IL-4, particularly in the presence of the relevant coreceptor. 
      gammadelta T cells transferred with a TCR specific for the hematopoiesis-specific 
      mHag HA-2 in combination with CD8 displayed high antileukemic reactivity against 
      HA-2-expressing leukemic cells. These data show that transfer of alphabetaTCRs to 
      gammadelta T cells generated potent effector cells for immunotherapy of leukemia, 
      without the expression of potentially hazardous mixed TCR dimers.
FAU - van der Veken, Lars T
AU  - van der Veken LT
AD  - Laboratory of Experimental Hematology, Department of Hematology, Leiden 
      University Medical Center, Leiden, the Netherlands.
FAU - Hagedoorn, Renate S
AU  - Hagedoorn RS
FAU - van Loenen, Marleen M
AU  - van Loenen MM
FAU - Willemze, Roel
AU  - Willemze R
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JH
FAU - Heemskerk, Mirjam H M
AU  - Heemskerk MH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CD3 Complex)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
SB  - IM
MH  - CD3 Complex/biosynthesis/genetics/immunology
MH  - Gene Transfer Techniques
MH  - Genetic Engineering
MH  - HLA-A2 Antigen/immunology
MH  - HLA-B7 Antigen/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/methods
MH  - Leukemia/immunology/therapy
MH  - Receptors, Antigen, T-Cell, alpha-beta/biosynthesis/*genetics/*immunology
MH  - Receptors, Antigen, T-Cell, gamma-delta/biosynthesis/*genetics/*immunology
MH  - Retroviridae/genetics
MH  - T-Lymphocytes/*immunology
EDAT- 2006/03/17 09:00
MHDA- 2006/05/04 09:00
CRDT- 2006/03/17 09:00
PHST- 2006/03/17 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2006/03/17 09:00 [entrez]
AID - 66/6/3331 [pii]
AID - 10.1158/0008-5472.CAN-05-4190 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Mar 15;66(6):3331-7. doi: 10.1158/0008-5472.CAN-05-4190.