Abstract 1581: Identification of novel HLA-restricted T-cell epitopes specific for the breast cancer-associated tumor antigen NY-BR-1

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.1581-1581
• Main Authors: Gardyan, Adriane, Osen, Wolfram, Jesiak, Maria, Zörnig, Inka, Jaeger, Dirk, Eichmueller, Stefan B.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-1581

Out of all malignancies, breast cancer resembles the most common malignant caner type (26%) of women in the western world and the second most frequent cancer related cause of death (15%) in women. Efficient treatment options are available for early stage breast cancers yielding five year survival rates of up to 85%, however for metastasized breast cancer types, five year survival rates are resided at much lower levels (20%) and therapy options are very limited. It is therefore of great importance to establish innovative therapy strategies which will affect the late stage breast cancer tumors. Immunotherapy approaches, particularly adoptive T cell transfer, constitute an attractive strategy to develop new therapy options for metastasized mammary carcinomas. The differentiation antigen NY-BR-1 was found to be expressed on mRNA level in breast tissue, testis, prostate, and most notably in 80% of tested breast cancers. Among normal tissues, expression of the NY-BR-1 protein was present solely in ductal epithelium of the breast. Compared to healthy breast tissue NY-BR-1 protein levels are highly elevated in invasive breast tumors and their corresponding metastasis. Thus, NY-BR-1 can be considered as a breast cancer associated tumor antigen that might represent a suitable target antigen for T cell based immunotherapy approaches. The main focus of this project is to identify novel HLA-restricted T cell epitopes that could be used in clinical trials. Therefore, various HLA-transgenic (tg) mouse strains (DR4tg, DR3tg and HHDtg mice), were immunized with the NY-BR-1- encoding expression plasmid pcDNA3.1-NY-BR-1 followed by ex vivo analyses of the NY-BR-1-specific T cell responses with a synthetic peptide library covering the entire NY-BR-1 protein. Applying this strategy, four potential HLA-DRB1*0301 restricted epitopes and three HLA-DRB*0401 restricted candidate epitopes could be determined. The relevance of these new epitopes for the human system will be analyzed by screening of PBMCs from tumor patients and healthy donors for the presence of cognate T cells. Such T cells will be expanded and used as donors for high affinity NY-BR-1-specific TCRs in order to establish autologous TCR-transduced T cells ready for adoptive transfer of breast cancer patients. Currently, blood-samples of NY-BR-1+ patients are being collected for subsequent in vitro analyses of HLA-restricted, NY-BR-1-specific T cell responses. Citation Format: {Authors}. {Abstract title} [abstract]. In