30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)
Targeting cyclin D1 for mantle cell lymphoma
Journal for ImmunoTherapy of Cancer volume 3, Article number: P430 (2015)
Cyclin D1, an important component of cell cycle and a protein with known oncogenic potential, is over expressed in mantle cell lymphoma (MCL). MCL is a distinct clinical pathologic subtype of B cell non-Hodgkin's lymphoma often associated with poor prognosis. New therapeutic approaches based on boosting anti-tumor immunity are being developed. Targeting cyclin D1 for MCL is rendering an interesting target for immunotherapy. However, the knowledge on the frequency and profile of cyclin D1-specific T cells in MCL patients is fragmented. Here we show that both healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells covering numerous epitopes from the whole cyclin D1 protein. Cyclin D1-specific T cells secrete IFN-g and type 2 cytokines including IL-5 and IL-13. Additionally, DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8+ T cells that kill MCL tumors. Furthermore, a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb was developed. Targeting monocyte-derived human DCs in vitro with anti-CD40-cyclin D1 fusion protein expanded a broad repertoire of cyclin D1-specific CD4+ and CD8+ T cells. Therefore, cyclin D1 represents a good target for immunotherapy.