New generation dendritic cell vaccine for immunotherapy of acute myeloid leukemia

Abstract

Dendritic cell (DC)-based immunotherapy is a promising strategy for the elimination of minimal residual disease in patients with acute myeloid leukemia (AML). Particularly, patients with a high risk of relapse who are not eligible for hematopoietic stem cell transplantation could benefit from such a therapeutic approach. Here, we review our extensive studies on the development of a protocol for the generation of DCs with improved immunogenicity and optimized for the use in cell-based immunotherapy. This new generation DC vaccine combines the production of DCs in only 3 days with Toll-like receptor-signaling-induced cell maturation. These mature DCs are then loaded with RNA encoding the leukemia-associated antigens Wilm's tumor protein 1 and preferentially expressed antigen in melanoma in order to stimulate an AML-specific T-cell-based immune response. In vitro as well as in vivo studies demonstrated the enhanced capacity of these improved DCs for the induction of tumor-specific immune responses. Finally, a proof-of-concept Phase I/II clinical trial is discussed for post-remission AML patients with high risk for disease relapse.

Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer

“…It is unclear why pancreatic cancer is poorly amenable to current immune-based therapies, but the ability to bolster an endogenous tumor-reactive T cell response may be critical to advance treatment outcome. Anti-tumor immune responses can be achieved by DC vaccines in a number of cancers, including melanoma [45–47], hepatocellular carcinoma [48], glioblastoma [49], castration-resistant prostate cancer [50, 51], renal cell carcinoma [52], acute myeloid leukemia (AML) [53], non-small cell lung cancer [54], pancreatic cancer [55, 56], and in various infectious diseases including hepatitis C virus [57] and HIV infection [58]. …”

Individualized vaccination of AML patients in remission is associated with induction of antileukemia immunity and prolonged remissions

“…However, to our knowledge, there are presently no vaccines that have shown promise in the treatment of AML. Strategies to design AML vaccines have included single antigen–based approaches, such as WT1 peptide administered with adjuvant (13, 14), DCs loaded with tumor-associated antigens (15, 16), or the use of AML cells differentiated into DCs (17). Immune responses have been observed in several studies.…”

Analogue peptides for the immunotherapy of human acute myeloid leukemia

“…Dendritic cells may also offer a powerful vehicle to present modified peptides to the immune system in AML patients [99]. Combination therapies which include chemotherapy to reduce tumor load and immunotherapy to remove MRD are expected to be superseded by conventional therapies used in conjunction with combination-immunotherapy protocols including the vaccination of patients with peptides following adoptive T-cell transfer [100] to remove residual disease.…”