Response of established human breast tumors to vaccination with mammaglobin-A cDNA

Journal of the National Cancer Institute
Kishore NarayananT Mohanakumar

Abstract

A novel breast cancer-associated antigen, mammaglobin-A, is expressed in 80% of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer-specific antigen would be of value in the development of new therapeutic strategies for breast cancer. We developed an in vivo model using human leukocyte antigen-A*0201/human CD8+ (HLA-A2+/hCD8+) double-transgenic mice to define the epitopes and to study the level of protection acquired by mammaglobin-A cDNA vaccination toward mammaglobin-A+/HLA-A2+ breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide binding prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. We identified seven mammaglobin-A-derived candidate epitopes that bind the HLA-A*0201 molecule (Mam-A2.1-7). CD8+ cytotoxic T lymphocytes (CTLs) from HLA-A2+/hCD8+ mice reacted to the Mam-A2.1 (amino acids [aa] 83-92, LIYDSSLCDL), Mam-A2.2 (aa 2-10, KLLMVLMLA), Mam-A2.4 (aa 66-74, FLNQTDETL), and Mam-A2.6 (aa 32-40, MQLIYDSSL) epitopes. CD8+ CTLs from breast cancer patients also recognized a similar epitope pattern as did those in the HLA-A2+/hCD8 mice and reacted to the Mam-A2.1, M...Continue Reading

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Citations

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