Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Hematological malignancies are cancers that affect blood and different organs like bone marrow and lymph nodes. Considering the close relationship between the immune system cells, a disease disturbing one of the three compartments will often influence the others as well [1]. While unusual in solid tumors, chromosomal translocations are a common cause of liquid tumors. This feature leads to a different approach in diagnosis and treatment of hematological malignancies [2]. AML is a type of hematological malignancies characterized by heterogeneous clonal disorder of hematopoietic progenitor cells and the most common acute leukemia in adults, with a poor prognosis and an overall survival rate of only 23.6 % at 5 years [3, 4]. It is also known by an increase in the number of myeloid cells in the marrow and an arrest in their maturation, frequently resulting in hematopoietic insufficiency (i.e. granulocytopenia, thrombocytopenia, or anemia) with or without leukocytosis [5]. Recent studies have revealed that the heterogeneity of malignant cells relates to the previously defined immature progenitors within the bulk of leukemic cells which are intrinsically resistant to chemotherapy and are able to repopulate the stem cells [6]. These newly-adopted "leukemia stem cells (LSCs)" share the most relevant features of the normal hematopoetic stem cells (HSCs) such as the selfrenewal potential and dormant status. It would be difficult to find various pools of leukemic stem cells within the individual patients which differ both phenotypically and molecularly [7, 8]. Despite intensive consolidation chemotherapy in AML patients, the relapses occur in 50% of the patients due to the presence of minimal residual disease (MRD) [3, 9, 10]. Since leukemic stem cells are thought to consist the most of cell population in MRDs, their study also has potentially promising clinical implications. On the other hand, while achieving complete remission (CR) mainly depends on high-dose chemotherapy, the maintenance protocols as well as different strategies for the induction or restoration of the immune pressure against LSCs are needed for several months or years after intensive chemotherapies [3]. Based on the major role of the immune system in the prevention and control of leukemia, alternative therapeutic approaches other than intensive chemotherapy or hematopoietic stem cell transplantation (HSCT) have been explored to modulate the immune system [1, 11, 12]. ABSTRACT Acute myeloid leukemia (AML) is a type of poor prognosis hematological malignancies characterized by heterogeneous clonal expansion of myeloid progenitors. Leukemic stem cells are thought to form the majority of a cell population in minimal residual diseases (MRDs) which are resistant to current chemotherapeutic regimens and mediate disease relapse. Current therapeutic vaccine strategies have developed to mount effective antileukemic immunity and eradicate the MRDs. Dendritic cells (DCs) are the most professional antigen-presenting cells to elicit efficient anti-leukemic immune responses. In this review article, we present the possibility of generating AML blast-targeted DCs, especially leukemia-derived DCs and their appropriate maturation protocols and particularly the synergistic effects of TLR agonists. We also discuss about the in vitro evaluation of the generated DCs, some reported outcomes of DC-based clinical trials as well as the possibility of combination therapy to improve the efficacy of DC-based vaccines in AML patients.