Specific immune responses against epitopes derived from Aurora kinase A and B in acute myeloid leukemia

Abstract

Aurora kinases are serine/threonine kinases which play an important role in the process of mitosis and cell cycle regulation. Aurora kinase inhibitors are described to sensitize malignant cells to cytosine arabinoside and specific antibodies by mediating apoptosis. Aurora kinases are overexpressed in most acute leukemias but also in solid tumors. In this study we investigated whether epitopes derived from Aurora kinase A and B are able to elicit cellular immune responses in patients with acute myeloid leukemia (AML) to investigate their role as potential targets for specific immunotherapy. Samples of eight patients with AML were analyzed in enzyme-linked immunosorbent spot (ELISpot) assays and compared with immune responses of nine healthy volunteers (HVs). Specific CD8 + T cell responses were detected against the epitopes Aura A1, A2, B1, B2, B3, B4 and B5. Immune responses for epitopes derived from Aura B were induced more frequently compared to Aura A. The antigens with the most frequent cytotoxic T-lymphocyte (CTL) responses were Aura B3, B4 and B5, although the number of patients tested for these antigens was low. Aura B5 did not elicit specific CTL responses in HVs. For epitope Aura B6 no immune response was detected in HVs or patients. Taken together, with the combination of Aurora kinase inhibitors and an immunotherapeutic approach, an effective blast and minimal residual disease elimination might be achieved.

Keywords::

• Acute myeloid leukemia (AML)
• immunotherapy
• Aurora kinases

Acknowledgements

This work was supported by grants from the German José Carreras Leukemia Foundation (DJCLS A 10/01 and R 10/03), the German Research Foundation (DFG GR2676/3-1) and the Else Kröner-Fresenius Stiftung (2011-A63).

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.