Abstract
Aurora kinase A (Aurora-A) is a cell cycle-associated serine-threonine kinase that is overexpressed by various types of cancer and is highly associated with poor prognosis. Since the expression of Aurora-A in normal tissues has been shown to be significantly lower as compared to tumor cells, this protein is being considered as a potential tumor-associated antigen for developing immunotherapies. The goal in the present study was to identify CD4 helper T lymphocyte (HTL) epitopes for Aurora-A for the design of T cell-based immunotherapies against Aurora-A-expressing tumors. Synthetic peptides corresponding to potential HTL epitopes were identified from Aurora-A and used to stimulate CD4 T lymphocytes in vitro to generate antigen-specific HTL clones that were evaluated for antigen specificity, MHC restriction and for their ability to interact with Aurora-A-expressing tumor cells. The results show that two peptides (Aurora-A161-175 and Aurora-A233-247) were effective in generating HTL responses that were restricted by more than one MHC class II allele (i.e., promiscuous responses). The CD4 HTL clones were able to directly recognize Aurora-A-expressing tumor cells in an antigen-specific and MHC class II-restricted manner and some of the clones displayed cytolytic activity toward Aurora-A + tumor cells. Both of these peptides were capable of stimulating in vitro T cell responses in patients with bladder cancer.
Original language | English (US) |
---|---|
Pages (from-to) | 1029-1039 |
Number of pages | 11 |
Journal | Cancer Immunology, Immunotherapy |
Volume | 59 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2010 |
Externally published | Yes |
Keywords
- Aurora kinase A
- CD4 helper T lymphocytes
- Immunotherapy
- Major histocompatibility complex class II
- Tumor antigens
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
- Cancer Research