PMID- 16365597
OWN - NLM
STAT- MEDLINE
DCOM- 20060201
LR  - 20191109
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 29
IP  - 1
DP  - 2006 Jan-Feb
TI  - Target antigen expression on a professional antigen-presenting cell induces 
      superior proliferative antitumor T-cell responses via chimeric T-cell receptors.
PG  - 21-31
AB  - Human T cells expressing tumor antigen-specific chimeric receptors fail to 
      sustain their growth and activation in vivo, which greatly reduces their 
      therapeutic value. The defective proliferative response to tumor cells in vitro 
      can partly be overcome by concomitant CD28 costimulatory signaling. We 
      investigated whether T-cell activation via chimeric receptors (chRec) can be 
      further improved by ligand expression on antigen-presenting cells of B-cell 
      origin. We generated Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes 
      (CTLs) expressing a CD19-specific chRec. These CTLs are provided with native 
      receptor stimulation by autologous EBV-transformed B-lymphoblastoid cell lines 
      (LCLs) but exclusively with chRec (CD19-specific) stimulation by allogeneic, 
      human leukocyte antigen (HLA)-mismatched CD19+ LCLs. CD19zeta-transduced 
      EBV-specific CTLs specifically lysed both allogeneic EBV targets and CD19+ tumor 
      cells through the chRec in a major histocompatibility complex-independent manner, 
      while maintaining their ability to recognize autologous EBV targets through the 
      native T-cell receptor. The transduced CTLs failed to proliferate in response to 
      CD19+ tumor targets even in the presence of CD28 costimulatory signaling. By 
      contrast, CD19 expressed on HLA-mismatched LCL-induced T-cell activation and 
      long-term proliferation that essentially duplicated the result from native 
      receptor stimulation with autologous LCLs, suggesting that a deficit of 
      costimulatory molecules on target cells in addition to CD28 is indeed responsible 
      for inadequate chRec-mediated T-cell function. Hence, effective tumor 
      immunotherapy may be favored if engagement of the chRec on modified T cells is 
      complemented by interaction with multiple costimulator molecules. The use of T 
      cells with native specificity for EBV may be one means of attaining this 
      objective.
FAU - Rossig, Claudia
AU  - Rossig C
AD  - Department of Pediatric Hematology and Oncology, University Children's Hospital 
      Munster, Munster, Germany. rossig@uni-muenster.de
FAU - Bar, Annette
AU  - Bar A
FAU - Pscherer, Sibylle
AU  - Pscherer S
FAU - Altvater, Bianca
AU  - Altvater B
FAU - Pule, Martin
AU  - Pule M
FAU - Rooney, Cliona M
AU  - Rooney CM
FAU - Brenner, Malcolm K
AU  - Brenner MK
FAU - Jurgens, Heribert
AU  - Jurgens H
FAU - Vormoor, Josef
AU  - Vormoor J
LA  - eng
GR  - P01 CA094237/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD19)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Antigen-Presenting Cells/*immunology
MH  - Antigens, CD19/immunology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Genetic Engineering/methods
MH  - Herpesvirus 4, Human/genetics/immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/methods
MH  - Leukemia, B-Cell/drug therapy/*immunology
MH  - Lymphocyte Activation/immunology
MH  - Receptors, Antigen, T-Cell/*genetics/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology/virology
MH  - Transduction, Genetic
EDAT- 2005/12/21 09:00
MHDA- 2006/02/02 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/02/02 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - 00002371-200601000-00003 [pii]
AID - 10.1097/01.cji.0000175492.28723.d6 [doi]
PST - ppublish
SO  - J Immunother. 2006 Jan-Feb;29(1):21-31. doi: 10.1097/01.cji.0000175492.28723.d6.