OncoImmunology | |
A blood dendritic cell vaccine for acute myeloid leukemia expands anti-tumor T cell responses at remission | |
Georgina J. Clark1  Phillip D. Fromm1  Michael S. Papadimitrious1  Benjamin Kong1  Jennifer L. Hsu1  Derek NJ Hart1  Robin E. Gasiorowski1  Christian E. Bryant1  Barbara Fazekas de St Groth2  Helen M. McGuire2  John Gibson3  P. Joy Ho3  Daniel Orellana3  Harry J. Iland3  Douglas E. Joshua3  Stephen Larsen3  | |
[1] ANZAC Research Institute;Charles Perkins Centre, The University of Sydney;Institute of Haematology, Royal Prince Alfred Hospital; | |
关键词: acute myeloid leukemia; blood dendritic cell; immunotherapy; allogeneic haematopoietic stem cell transplantation; chemotherapy; t cell landscape; checkpoint inhibitor; | |
DOI : 10.1080/2162402X.2017.1419114 | |
来源: DOAJ |
【 摘 要 】
Only modest advances in AML therapy have occurred in the past decade and relapse due to residual disease remains the major challenge. The potential of the immune system to address this is evident in the success of allogeneic transplantation, however this leads to considerable morbidity. Dendritic cell (DC) vaccination can generate leukemia-specific autologous immunity with little toxicity. Promising results have been achieved with vaccines developed in vitro from purified monocytes (Mo-DC). We now demonstrate that blood DC (BDC) have superior function to Mo-DC. Whilst BDC are reduced at diagnosis in AML, they recover following chemotherapy and allogeneic transplantation, can be purified using CMRF-56 antibody technology, and can stimulate functional T cell responses. While most AML patients in remission had a relatively normal T cell landscape, those who had received fludarabine as salvage therapy have persistent T cell abnormalities including reduced number, altered subset distribution, failure to expand, and increased activation-induced cell death. Furthermore, PD-1 and TIM-3 are increased on CD4T cells in AML patients in remission and their blockade enhances the expansion of leukemia-specific T cells. This confirms the feasibility of a BDC vaccine to consolidate remission in AML and suggests it should be tested in conjunction with checkpoint blockade.
【 授权许可】
Unknown