Recently, the cell cycle-related protein cyclin B1 has been discovered to contain immunostimulatory peptides that are expressed on lung tumor cells. These peptides were identified using dendritic cells and peptides eluted from HLA-class I molecules of tumor cells as a tumor antigen discovery system. Several peptide fractions analyzed within this project, which had immunostimulatory properties, were found to contain 9 and 10 amino acid long peptides all derived from cyclin B1. Cytotoxic T cells derived by priming on dendritic cells loaded with those peptides killed tumor cells but not normal cells. Upon examination of cyclin B1 expression in tumor cells, it was found that tumor cells overexpress this protein, and moreover, it is localized in the cytoplasm, rather than in the nucleus.
Normal cells show low amounts and nuclear localization.
I restricted cytotoxic T lymphocytes. Dr. Finn s laboratory is working to further explore this antigenic difference between tumor cells and normal cells and to apply the results clinically, with the goal of producing a dendritic cell based lung cancer vaccine. Her studies have previously shown that most lung tumors express the protein c-Met, which is the receptor for HGF, and that the stromal cells within lung tumors produce HGF, which enhances migration and proliferation of tumor cells. In an ongoing prospective study, Dr. Siegfried and coworkers are measuring HGF levels in newly diagnosed patients and determining whether outcome can be predicted. This is especially important for Stage I patients who otherwise are not placed on treatment regimens, but who could be placed in a high-risk group based on the HGF results.