PMID- 19561534
OWN - NLM
STAT- MEDLINE
DCOM- 20090925
LR  - 20201219
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 32
IP  - 7
DP  - 2009 Sep
TI  - A novel mouse model for evaluation and prediction of HLA-A2-restricted CEA cancer 
      vaccine responses.
PG  - 744-54
LID - 10.1097/CJI.0b013e3181aee1b6 [doi]
AB  - Human leukocyte antigen (HLA)-A2.1 transgenic mice (HHD) represent a valuable 
      model to study and predict the immunogenicity of vaccines against pathogens. 
      However, HHD mice are unsuitable for in vivo studies of cancer vaccines against 
      human tumor-associated antigens because they lack T-cell tolerance that is key to 
      define the potency of the treatment. In this study, we developed 
      HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice 
      homozygous for CEA with HHD. These mice express human CEA, present epitopes 
      solely through HLA-A2.1 molecules and constitute a unique in vivo animal model to 
      study HLA-A2.1-restricted immune response of a human CEA-based vaccine. Owing to 
      the immune tolerance, HHD/CEA mice show a limited immune response and expansion 
      of a different and restricted T-cell receptor repertoire after antigen-specific 
      stimulation. Our data show that genetic vectors expressing CEA and peptide-based 
      vaccines are able to efficiently break immune tolerance against CEA and to elicit 
      strong immune response against HLA-A2.1-restricted CEA epitopes. Most 
      importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and 
      significant protection against HHD/CEA tumor cells was achieved in 
      HHD/CEA-vaccinated mice. Hence, HHD/CEA provides a relevant model for the 
      evaluation of the potential efficacy of human CEA-based vaccines.
FAU - Conforti, Antonella
AU  - Conforti A
AD  - Department of Oncology, I.R.B.M. P. Angeletti, Pomezia, Italy.
FAU - Peruzzi, Daniela
AU  - Peruzzi D
FAU - Giannetti, Patrizia
AU  - Giannetti P
FAU - Biondo, Antonella
AU  - Biondo A
FAU - Ciliberto, Gennaro
AU  - Ciliberto G
FAU - La Monica, Nicola
AU  - La Monica N
FAU - Aurisicchio, Luigi
AU  - Aurisicchio L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cancer Vaccines)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Epitopes)
RN  - 0 (H-2 Antigens)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Cancer Vaccines/administration & dosage/*immunology
MH  - Carcinoembryonic Antigen/genetics/*immunology/metabolism
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic/immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/immunology
MH  - Feces/chemistry
MH  - Female
MH  - Flow Cytometry
MH  - Gastrointestinal Tract/metabolism
MH  - H-2 Antigens/immunology
MH  - HLA-A2 Antigen/genetics/*immunology/metabolism
MH  - Humans
MH  - Male
MH  - Melanoma, Experimental/*immunology/pathology/prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell/immunology/metabolism
MH  - Transfection
MH  - Vaccination/methods
EDAT- 2009/06/30 09:00
MHDA- 2009/09/26 06:00
CRDT- 2009/06/30 09:00
PHST- 2009/06/30 09:00 [entrez]
PHST- 2009/06/30 09:00 [pubmed]
PHST- 2009/09/26 06:00 [medline]
AID - 10.1097/CJI.0b013e3181aee1b6 [doi]
PST - ppublish
SO  - J Immunother. 2009 Sep;32(7):744-54. doi: 10.1097/CJI.0b013e3181aee1b6.