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@ARTICLE{Gardyan:126568,
author = {A. Gardyan$^*$ and W. Osen$^*$ and I. Zörnig$^*$ and L.
Podola$^*$ and M. Agarwal$^*$ and S. Aulmann and E.
Ruggiero$^*$ and M. Schmidt$^*$ and N. Halama$^*$ and B.
Leuchs$^*$ and C. von Kalle$^*$ and P. Beckhove$^*$ and A.
Schneeweiss and D. Jäger$^*$ and S. Eichmüller$^*$},
title = {{I}dentification of {NY}-{BR}-1-specific {CD}4(+) {T} cell
epitopes using {HLA}-transgenic mice.},
journal = {International journal of cancer},
volume = {136},
number = {11},
issn = {0020-7136},
address = {Bognor Regis},
publisher = {Wiley-Liss},
reportid = {DKFZ-2017-02596},
pages = {2588 - 2597},
year = {2015},
abstract = {Breast cancer represents the second most common cancer type
worldwide and has remained the leading cause of
cancer-related deaths among women. The differentiation
antigen NY-BR-1 appears overexpressed in invasive mammary
carcinomas compared to healthy breast tissue, thus
representing a promising target antigen for T cell based
tumor immunotherapy approaches. Since efficient immune
attack of tumors depends on the activity of tumor
antigen-specific CD4(+) effector T cells, NY-BR-1 was
screened for the presence of HLA-restricted CD4(+) T cell
epitopes that could be included in immunological treatment
approaches. Upon NY-BR-1-specific DNA immunization of
HLA-transgenic mice and functional ex vivo analysis, a panel
of NY-BR-1-derived library peptides was determined that
specifically stimulated IFNγ secretion among splenocytes of
immunized mice. Following in silico analyses, four candidate
epitopes were determined which were successfully used for
peptide immunization to establish NY-BR-1-specific,
HLA-DRB1*0301- or HLA-DRB1*0401-restricted CD4(+) T cell
lines from splenocytes of peptide immunized HLA-transgenic
mice. Notably, all four CD4(+) T cell lines recognized human
HLA-DR-matched dendritic cells (DC) pulsed with lysates of
NY-BR-1 expressing human tumor cells, demonstrating natural
processing of these epitopes also within the human system.
Finally, CD4(+) T cells specific for all four CD4(+) T cell
epitopes were detectable among PBMC of breast cancer
patients, showing that CD4(+) T cell responses against the
new epitopes are not deleted nor inactivated by
self-tolerance mechanisms. Our results present the first
NY-BR-1-specific HLA-DRB1*0301- and HLA-DRB1*0401-restricted
T cell epitopes that could be exploited for therapeutic
intervention against breast cancer.},
keywords = {Antigens, Neoplasm (NLM Chemicals) / Epitopes, T-Lymphocyte
(NLM Chemicals) / HLA-DRB1 Chains (NLM Chemicals) /
HLA-DRB1*03:01 antigen (NLM Chemicals) / HLA-DRB1*04:01
antigen (NLM Chemicals) / Peptide Library (NLM Chemicals) /
breast cancer antigen NY-BR-1, human (NLM Chemicals) /
Interferon-gamma (NLM Chemicals)},
cin = {D015 / D120 / G100 / F010 / G010 / G183 / G182},
ddc = {610},
cid = {I:(DE-He78)D015-20160331 / I:(DE-He78)D120-20160331 /
I:(DE-He78)G100-20160331 / I:(DE-He78)F010-20160331 /
I:(DE-He78)G010-20160331 / I:(DE-He78)G183-20160331 /
I:(DE-He78)G182-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25387692},
doi = {10.1002/ijc.29322},
url = {https://inrepo02.dkfz.de/record/126568},
}