Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 744-754 |
| Number of pages | 11 |
| Journal | Journal of Immunotherapy |
| Volume | 32 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Sep 2009 |
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Keywords
- Cancer vaccine
- CEA
- HLA-A2.1
- Tolerance
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Cancer Research
- Pharmacology
Cite this
A novel mouse model for evaluation and prediction of HLA-A2-restricted CEA cancer vaccine responses. / Conforti, Antonella; Peruzzi, Daniela; Giannetti, Patrizia; Biondo, Antonella; Ciliberto, Gennaro; Monica, Nicola La; Aurisicchio, Luigi.
In: Journal of Immunotherapy, Vol. 32, No. 7, 09.2009, p. 744-754.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel mouse model for evaluation and prediction of HLA-A2-restricted CEA cancer vaccine responses
AU - Conforti, Antonella
AU - Peruzzi, Daniela
AU - Giannetti, Patrizia
AU - Biondo, Antonella
AU - Ciliberto, Gennaro
AU - Monica, Nicola La
AU - Aurisicchio, Luigi
PY - 2009/9
Y1 - 2009/9
N2 - 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.
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.
KW - Cancer vaccine
KW - CEA
KW - HLA-A2.1
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=68449088812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68449088812&partnerID=8YFLogxK
U2 - 10.1097/CJI.0b013e3181aee1b6
DO - 10.1097/CJI.0b013e3181aee1b6
M3 - Article
C2 - 19561534
AN - SCOPUS:68449088812
VL - 32
SP - 744
EP - 754
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1053-8550
IS - 7
ER -