Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a type of blood cancer characterized by the uncontrolled clonal proliferation of myeloid hematopoietic progenitor cells in the bone marrow. The outcome of AML is poor, with five-year overall survival rates of less than 10% for the predominant group of patients older than 65 years. One of the main reasons for this poor outcome is that the majority of AML patients will relapse, even after they have attained complete remission by chemotherapy. Chemotherapy, supplemented with allogeneic hematopoietic stem cell transplantation in patients at high risk of relapse, is still the cornerstone of current AML treatment. Both therapies are, however, associated with significant morbidity and mortality. These observations illustrate the need for more effective and less toxic treatment options, especially in elderly AML and have fostered the development of novel immune-based strategies to treat AML. One of these strategies involves the use of a special type of immune cells, the dendritic cells (DCs). As central orchestrators of the immune system, DCs are key to the induction of anti-leukemia immunity. In this review, we provide an update of the clinical experience that has been obtained so far with this form of immunotherapy in patients with AML.

Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

“…Specific surface markers including CD11c + , CD86, and the MHCII family MHCII (I-A) were highly expressed in this work, indicating that mouse bone marrow-derived monocytes differentiated into mature DCs. Mature DCs can strongly promote anticancer immunity and trigger Th1/Th17 cytokine secretion [8,32,33,42,46]. The close relationship between IL-4 and tumor progression has been investigated in several diseases [41,42].…”

“…Mature DCs can strongly promote anticancer immunity and trigger Th1/Th17 cytokine secretion [8,32,33,42,46]. The close relationship between IL-4 and tumor progression has been investigated in several diseases [41,42]. IL-6 overexpression is present in numerous cancer types, leading to the dysregulation of a plethora of cellular activities that generally promote tumor progression [37].…”

Is Hematopoietic Stem Cell Transplantation Required to Unleash the Full Potential of Immunotherapy in Acute Myeloid Leukemia?

“…Dendritic cell (DC) vaccines have been the most common strategy to target AML intracellular antigens, with a wide range of manufacturing strategies and targets explored [87]. DCs loaded with AML antigens are able to stimulate T and NK cells to induce an antileukemia effect [88].…”

“…The main advantage of DC vaccination is the demonstrated favorable safety profile, which is especially important given the advanced average age at presentation [88]. The main barriers to entering routine clinical practice are the variability across different strategies and limited efficacy [87]. The type of DC used may be one of the limiting factors in vaccination efficacy.…”

Conjugation of TLR7 Agonist Combined with Demethylation Treatment Improves Whole-Cell Tumor Vaccine Potency in Acute Myeloid Leukemia

“…Minimal residue disease (MRD), a small reservoir of treatment-resistant leukemic cells that persist after chemotherapy, is an important risk factor for the poor prognosis of AML and often accounts for the relapse of the disease 11 . Allogeneic hematopoietic stem cell transplantation (HSCT) can be used to clear MRD effectively and has a positive impact on relapse rate and survival 12 . However, HSCT is still associated with relatively high morbidity and mortality rate, resulting in the limitation of its application in relatively younger patients who generally have fewer co-morbidities 13 .…”