Recent Advances in Antigen-Loaded Dendritic Cell-Based Strategies for Treatment of Minimal Residual Disease in Acute Myeloid Leukemia

Abstract

Therapeutic vaccination with dendritic cells (DCs) is recognized as an important experimental therapy for the treatment of minimal residual disease in acute myeloid leukemia. Many sources of leukemia-associated antigens and different methods for antigen loading of DCs have been used in an attempt to optimize anti-tumor responses. For instance, monocyte-derived DCs have been loaded with apoptotic whole-cell suspensions, necrotic cell lysates, tumor-associated peptides, eluted peptides and cellular DNA or RNA. Furthermore, monocyte-derived DCs can be chemically or electrically fused with leukemic blasts, and DCs have been cultured out of leukemic blasts. However, it remains a challenge in cancer immunotherapy to identify which of these methods is the most optimal for antigen loading and activation of DCs. This review discusses recent advances in DC research and the application of this knowledge towards new strategies for antigen loading of DCs in the treatment of minimal residual disease in acute myeloid leukemia.

Priming of PRAME- and WT1-specific CD8+T cells in healthy donors but not in AML patients in complete remission

“…DC-based vaccination aims at eliciting a leukemia-associated antigen (LAA)-specific immune response against residual leukemic cells, thus preventing relapse 1 . In this respect, peptides carrying defined LAA-epitopes are an attractive source of antigens.…”

Dendritic Cells in Cord Blood Transplantation: A Review

“…The applications of immunotherapeutic DC vaccination, as a way of enhancing host anticancer immunity, is another developing field; the administration of DC loaded with leukemic cell antigens is a promising experimental treatment for minimal residual disease in acute myeloid leukemia and was the focus of a recent review by Van Den Ancker et al [21]. …”

Disease-Free Remission Exceeding 37 Years in Patients Treated as Children for Acute Leukemia (AL) with Immunotherapy Using Viable (Cryopreserved) Allogeneic Leukemic Cells Pages 254-26

“…It's very difficult to eradicate minimal residual leukemic cells (MRD) during the period of remission using modern modalities of therapy. Therefore, a constant threat of fatal relapse is always present [1][2]. Forty five years ago, i.e., in 1967, when we started our investigations, the efficacy of chemotherapy in children with AL using 6-Mercaptopurine (6-MP), Vincristine (V), Methotrexate (MTX) and Prednisolone (P) was significantly lower than now.…”

“…maximal immunogenicity and specificity of the injected antigen, 2. minimal mass of the tumor 3. the ability of the patient's organism to mount an adequate response to an injected antigen.…”

“…(Still earlier the difference Patients from treatment group in a continued remission between LAA during AML and ALL had been demonstrated [33][34][35]). Among the methods of immunotherapy there are great hopes from the use of peptide vaccines and derivates and modifications of dendritic cells [2,[36][37][38][39][40][41], however only few of those studies are concerned with AML [42][43][44][45]. All that serves as evidence of the justifiability of searching for rational methods of immunotherapy for recovery from AL.…”