HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice

Item Type:	Article
Title:	HER-2/neu mediated down-regulation of MHC class I antigen processing prevents CTL-mediated tumor recognition upon DNA vaccination in HLA-A2 transgenic mice
Creators Name:	Vertuani, S. and Triulzi, C. and Roos, A.K. and Charo, J. and Norell, H. and Lemonnier, F. and Pisa, P. and Seliger, B. and Kiessling, R.
Abstract:	To study DNA vaccination directed against human HER-2 in the HHD mouse Tg strain, we created a novel HER-2-expressing syngeneic tumor transplantation model. We found that a DNA vaccine encoding the full length HER-2 DNA protected HHD mice from HER-2(+) tumor challenge by a CTL independent mechanism. A more efficient approach to induce HLA-A2 restricted CTLs, through immunization with a multi-epitope DNA vaccine expressing the HLA-A2 restricted HER-2 369-377, 435-443 and 689-697 epitopes, resulted in high numbers of peptide specific T cells but failed to induce tumor protection. Subsequently we discovered that HER-2 transfected tumor cells down-regulated MHC class I antigen expression and exhibited a series of defects in the antigen processing pathway which impaired the capacity to produce and display MHC class I peptide-ligands to specific CTLs. Our data demonstrate that HER-2 transfection is associated with defects in the MHC class I presentation pathway, which may be the underlying mechanism behind the inability of CTLs to recognize tumors in this HLA-A2 transgenic model. As defective MHC class I presentation may be a common characteristic of HER-2 expressing tumors, vaccines targeting HER-2 should aim at inducing an integrated immune response where also CD4(+) T cells and antibodies are important components.
Keywords:	DNA Vaccine, HER-2, MHC Class I, Antigen Processing, Animals, Mice
Source:	Cancer Immunology Immunotherapy
ISSN:	0340-7004
Publisher:	Springer
Volume:	58
Number:	5
Page Range:	653-664
Date:	May 2009
Official Publication:	https://doi.org/10.1007/s00262-008-0587-1
PubMed:	View item in PubMed

Repository Staff Only: item control page