Genetic vaccines against Ep-CAM break tolerance to self in a limited subset of subjects: initial identification of predictive biomarkers
| Autor: | Francesco Calvaruso, Fabio Palombo, Leonardo Elia, Valentina Salucci, Alessia Scarito, Mariangela Storto, Carmela Mennuni, Gennaro Ciliberto, Silvia Podda, Nicola La Monica, Luigi Aurisicchio |
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| Rok vydání: | 2006 |
| Předmět: |
Immunology
Molecular Sequence Data Biology Inbred C57BL Major histocompatibility complex Cancer Vaccines Immune tolerance Adenoviridae Mice Immune system Antigen Antigens Neoplasm MHC class I Cancer vaccine Tumor-associated antigen Immune Tolerance Vaccines DNA Inbred DBA Immunology and Allergy Animals Amino Acid Sequence Antigens Inbred BALB C Cell-mediated immune response Vaccines Mice Inbred BALB C Vaccines Synthetic ELISPOT Synthetic Vaccination DNA Epithelial Cell Adhesion Molecule Macaca mulatta Mice Inbred C57BL Mice Inbred DBA biology.protein Neoplasm Biomarkers Cell Adhesion Molecules |
| Zdroj: | European journal of immunology. 36(5) |
| ISSN: | 0014-2980 |
| Popis: | The epithelial cell adhesion molecule, Ep-CAM, has been historically considered a target of passive immunotherapy using monoclonal antibodies, and more recently, of a first Pox-vector-based cancer vaccine Phase I trial in colorectal cancer patients. To shed further light on the use of this antigen, we isolated the mouse and rhesus homologues of human Ep-CAM and explored different genetic vaccination modalities based on the use of adenoviral vectors as well as DNA electroporation (DNA-EP). Immune responses to Ep-CAM were measured by IFN-gamma ELISPOT and intracellular staining assays using overlapping sets of peptides covering the entire coding regions. We found the most powerful vaccination regimen to be constituted by DNA-EP-prime/Adeno-boost mixed-modality protocols. Vaccination in rhesus macaques resulted in breakage of immunological tolerance in a minority of cases. Similarly, a low frequency of responders was observed with the mouse Ep-CAM vaccine in outbred CD1 mice. When immunized CD1 mice were analyzed for MHC haplotype and TCR expression levels, we observed that immune responders all had the same q/q MHC class I haplotype and showed higher expression levels of the TCRVbeta4 and TCRVbeta8 T cell receptors. Our results underscore the current limitations in our capacity to induce efficient cancer vaccines against self antigens like Ep-CAM, but also represent a first effort to identify predictive biomarkers of response. |
| Databáze: | OpenAIRE |
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