PMID- 20386466
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20111117
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 33
IP  - 4
DP  - 2010 May
TI  - HLA-A*0201-restricted CEA-derived peptide CAP1 is not a suitable target for 
      T-cell-based immunotherapy.
PG  - 402-13
LID - 10.1097/CJI.0b013e3181d366da [doi]
AB  - Carcinoembryonic antigen (CEA) is a potential target for antigen-specific 
      immunotherapy, as it is frequently overexpressed in human carcinomas. Moreover, 
      an epitope derived from CEA, designated CAP1 (YLSGANLNL), has been proposed as 
      naturally processed and presented by tumors in the human leukocyte antigen 
      (HLA)-A*0201 context. Our aim was to fully characterize and assess the clinical 
      relevance of the HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) response 
      against CEA. Stable and potent artificial antigen presenting cells (AAPCs) were 
      used to evaluate T-cell response against CEA. These cells efficiently activate 
      CTLs against tumor-derived epitopes after transduction with the antigenic 
      peptides or full-length proteins. We found that AAPCs genetically modified to 
      express CAP1, the agonist peptide CAP1-6D, or the whole CEA protein were not able 
      to activate CAP1-specific CTLs from HLA-A*0201+ healthy donors or patients with 
      colorectal carcinoma, even after multiple stimulations. In addition, we showed 
      that a CAP1-specific T-cell clone, obtained after multiple stimulations of T 
      cells of a HLA-A*0201+ healthy donor in vitro with autologous antigen presenting 
      cells, recognized CEA(-) HLA-A*0201+ tumors transduced with a minigene encoding 
      CAP1 but failed to react against HLA-A*0201+ tumor cells expressing CEA. Finally, 
      AAPCs expressing the whole CEA protein did not induce any specific CTL response 
      against CEA+ HLA-A*0201+ tumor cells highlighting the potential difficulty of 
      mounting an efficacious T-cell response against this autoantigen. Altogether, our 
      data indicate that CAP1 is not efficiently processed and presented by CEA+ tumor 
      cells, and therefore, is not an appropriate target for T-cell-based 
      immunotherapy.
FAU - Fauquembergue, Emilie
AU  - Fauquembergue E
AD  - Inserm U614, Faculty of Medicine, Institute for Biomedical Research, University 
      Hospital, Rouen, France.
FAU - Toutirais, Olivier
AU  - Toutirais O
FAU - Tougeron, David
AU  - Tougeron D
FAU - Drouet, Aurelie
AU  - Drouet A
FAU - Le Gallo, Matthieu
AU  - Le Gallo M
FAU - Desille, Mireille
AU  - Desille M
FAU - Cabillic, Florian
AU  - Cabillic F
FAU - de La Pintiere, Cecile Thomas
AU  - de La Pintiere CT
FAU - Iero, Manuela
AU  - Iero M
FAU - Rivoltini, Licia
AU  - Rivoltini L
FAU - Baert-Desurmont, Stephanie
AU  - Baert-Desurmont S
FAU - Leprince, Jerome
AU  - Leprince J
FAU - Vaudry, Hubert
AU  - Vaudry H
FAU - Sesboue, Richard
AU  - Sesboue R
FAU - Frebourg, Thierry
AU  - Frebourg T
FAU - Latouche, Jean-Baptiste
AU  - Latouche JB
FAU - Catros, Veronique
AU  - Catros V
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (CAP1-6D)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Oligopeptides)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antigen Presentation
MH  - Carcinoembryonic Antigen/genetics/immunology/*metabolism
MH  - Carcinoma/immunology/pathology/*therapy
MH  - Cloning, Molecular
MH  - HLA-A Antigens/metabolism
MH  - HLA-A2 Antigen
MH  - HT29 Cells
MH  - Humans
MH  - *Immunotherapy, Adoptive
MH  - Lymphocyte Activation/genetics
MH  - Mice
MH  - Oligopeptides/genetics/immunology/*metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism/pathology
MH  - Transduction, Genetic
EDAT- 2010/04/14 06:00
MHDA- 2010/09/18 06:00
CRDT- 2010/04/14 06:00
PHST- 2010/04/14 06:00 [entrez]
PHST- 2010/04/14 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
AID - 10.1097/CJI.0b013e3181d366da [doi]
PST - ppublish
SO  - J Immunother. 2010 May;33(4):402-13. doi: 10.1097/CJI.0b013e3181d366da.