Genetic vaccines against Ep-CAM break tolerance to self in a limited subset of subjects: initial identification of predictive biomarkers

European Journal of Immunology
Leonardo EliaFabio Palombo

Abstract

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 u...Continue Reading

References

Apr 15, 1999·Cancer Immunology, Immunotherapy : CII·S MosolitsH Mellstedt
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·G RizzutoE Fattori
Dec 10, 1999·The Journal of Experimental Medicine·W B BowneA N Houghton
Dec 22, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M BalzarS V Litvinov
Jul 27, 2000·Annals of the New York Academy of Sciences·S BasakD Herlyn
Jul 27, 2001·Journal of Immunological Methods·H T MaeckerL J Picker
Oct 2, 2001·Critical Reviews in Oncology/hematology·L S Schwartzberg
Apr 4, 2003·International Journal of Cancer. Journal International Du Cancer·Dirk NagorsenUlrich Keilholz
Sep 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Thai M CaoJudith A Shizuru
Sep 26, 2003·Cancer Biology & Therapy·Andrew Armstrong, Stephen L Eck
Jan 28, 2004·Human Pathology·Philip Th WentStephan Dirnhofer
Apr 20, 2004·Journal of Translational Medicine·Roopa Srinivasan, Jedd D Wolchok
Jul 29, 2004·Journal of Virology·Andrea FacciabeneNicola La Monica
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Pasquale GalloPaolo Monaci
Dec 1, 2004·Cancer Immunology, Immunotherapy : CII·Szilvia MosolitsMahmood Jeddi-Tehrani

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Citations

Feb 19, 2008·Molecular Cancer Therapeutics·Min LiQizhi Yao
Jun 22, 2011·Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association·Sílvia Regina Caminada ToledoAntonio Sergio Petrilli
Apr 7, 2010·Journal of Biomedicine & Biotechnology·Daniela FiorettiMonica Rinaldi
Apr 28, 2006·European Journal of Immunology·Freda K Stevenson, Jason Rice
Feb 16, 2019·Journal of Experimental & Clinical Cancer Research : CR·Luigi AurisicchioFabio Palombo

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