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Specific immune responses against epitopes derived from Aurora kinase A and B in acute myeloid leukemia
Vanessa Schneider1, Stephanie Egenrieder, Marlies Götz
1Department of Internal Medicine III, University of Ulm, Ulm, Germany.
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.
Insights
This study shows that specific T cell responses can be generated against Aurora kinase epitopes in acute myeloid leukemia (AML) patients. These findings suggest a potential role for Aurora kinase-targeted immunotherapy in AML treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Aurora kinases are crucial for mitosis and cell cycle regulation.
- Overexpressed in various cancers, including acute myeloid leukemia (AML).
- Aurora kinase inhibitors show potential in sensitizing cancer cells to therapies.
Purpose of the Study:
- To investigate if Aurora kinase A and B epitopes can elicit cellular immune responses in AML patients.
- To explore the potential of these epitopes as targets for specific immunotherapy.
- To compare immune responses in AML patients versus healthy volunteers.
Main Methods:
- Enzyme-linked immunosorbent spot (ELISpot) assays were used.
- Eight AML patients and nine healthy volunteers (HVs) were analyzed.
- Specific CD8+ T cell responses against Aurora kinase epitopes were measured.
Main Results:
- Specific CD8+ T cell responses were detected against multiple Aurora kinase epitopes (Aura A1, A2, B1-B5).
- Epitopes from Aurora kinase B induced immune responses more frequently than those from Aurora kinase A.
- Aura B3, B4, and B5 showed the most frequent cytotoxic T-lymphocyte (CTL) responses in AML patients.
Conclusions:
- Aurora kinase epitopes can elicit cellular immune responses in AML patients.
- Aurora kinase B-derived epitopes are promising targets for immunotherapy.
- Combining Aurora kinase inhibitors with immunotherapy may enhance blast and minimal residual disease elimination in AML.
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