PMID- 17606735
OWN - NLM
STAT- MEDLINE
DCOM- 20070906
LR  - 20070703
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 13
DP  - 2007 Jul 1
TI  - Rebuilding human leukocyte antigen class II-restricted minor histocompatibility 
      antigen specificity in recall antigen-specific T cells by adoptive T cell 
      receptor transfer: implications for adoptive immunotherapy.
PG  - 4009-15
AB  - PURPOSE: Donor T cells directed to hematopoietic minor histocompatibility 
      antigens (mHag) are appealing tools for adoptive immunotherapy of hematological 
      malignancies after allogeneic stem cell transplantation (allo-SCT). Toward the 
      development of a convenient strategy for ex vivo generation of human leukocyte 
      antigen (HLA) class II--restricted mHag-specific T cells, we evaluated the 
      feasibility of rebuilding mHag-specific T cell functions in donor-derived recall 
      antigen-specific T cells via T cell receptor (TCR) transfer. EXPERIMENTAL DESIGN: 
      TCR alpha- and beta-chains of an HLA-DPB1*0401--restricted T-cell clone 
      recognizing a multiple myeloma-associated mHag were retrovirally transferred into 
      a tetanus toxoid (TT)--specific clone derived from the original stem cell donor. 
      TCR double-transduced cells were compared with the parent mHag- and TT-specific 
      clones for antigen specificity, cytokine secretion, and cytotoxic activity and 
      were analyzed for their in vitro expansion capacity in a TT- or mHag-specific 
      fashion. RESULTS: mHag-TCR--transduced TT-specific cells displayed both TT and 
      mHag specificity. Similar to the parent cells, they secreted Th-1 cytokines and 
      exerted significant cytotoxic activity against TT-pulsed or mHag(+) target cells, 
      including multiple myeloma cells. A 4-week expansion of TCR-transduced cells via 
      the TT-specific TCR had no negative influence on the mHag-specific cytotoxic 
      activity and resulted in 10- to 100-fold better cell yields as compared with 
      mHag-specific expansion. CONCLUSIONS: HLA class II--restricted, mHag-specific 
      effector functions can be successfully reconstructed in donor-derived TT-specific 
      T cells via TCR transfer. Effective expansion of these T cells via TT-specific 
      TCRs illustrate the suitability of this strategy for ex vivo expansion and 
      possibly for in vivo TT-specific reboosting of HLA class II--restricted 
      immunotherapeutic T cells.
FAU - Spaapen, Robbert
AU  - Spaapen R
AD  - Authors' Affiliations: Departments of Clinical Chemistry and Haematology, 
      Immunology, and Haematology, University Medical Center Utrecht, the Netherlands.
FAU - van den Oudenalder, Kelly
AU  - van den Oudenalder K
FAU - Ivanov, Roman
AU  - Ivanov R
FAU - Bloem, Andries
AU  - Bloem A
FAU - Lokhorst, Henk
AU  - Lokhorst H
FAU - Mutis, Tuna
AU  - Mutis T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Minor Histocompatibility Antigens)
SB  - IM
MH  - Adoptive Transfer
MH  - Cell Line, Tumor
MH  - Cell Separation
MH  - Cell Transplantation
MH  - Cloning, Molecular
MH  - Flow Cytometry
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Immunophenotyping
MH  - Immunotherapy, Adoptive/*methods
MH  - Minor Histocompatibility Antigens/*chemistry
MH  - Multiple Myeloma/metabolism
MH  - Retroviridae/genetics
MH  - T-Lymphocytes/chemistry/*immunology
MH  - Time Factors
EDAT- 2007/07/04 09:00
MHDA- 2007/09/07 09:00
CRDT- 2007/07/04 09:00
PHST- 2007/07/04 09:00 [pubmed]
PHST- 2007/09/07 09:00 [medline]
PHST- 2007/07/04 09:00 [entrez]
AID - 13/13/4009 [pii]
AID - 10.1158/1078-0432.CCR-07-0286 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Jul 1;13(13):4009-15. doi: 10.1158/1078-0432.CCR-07-0286.