Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Wong, Kah Keng; Hassan, Rosline; Yaacob, Nik Soriani

doi:10.3389/fonc.2021.624742

Cited by 27 publications

(19 citation statements)

References 155 publications

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“…Studies have revealed that the combination of decitabine or guadecitabine with the NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients [ 145 , 146 ]. The de novo expressed NY-ESO-1 protein was naturally processed and presented in a time- and dose-dependent fashion up to 8 days after the start of DAC treatment, and converted the cell lines susceptible to antigen-specific recognition by CD8 + T cell clones [ 145 ].…”

Section: Enhancing DC Vaccine Efficacy Via Coadministration With Chemotherapy and Checkpoint Inhibitorsmentioning

confidence: 99%

“…T cells from AML patients treated with DC/AML cell fusion vaccine and guadecitabine displayed an increased capacity to lyse AML cells. In vitro studies also demonstrated that decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor T (CAR-T) cell antileukemic activities against AML [ 146 ]. In a phase I study, 9 patients with MDS received an HLA-unrestricted NY-ESO-1 vaccine on a nonoverlapping schedule every 4 weeks with standard-dose decitabine.…”

Section: Enhancing DC Vaccine Efficacy Via Coadministration With Chemotherapy and Checkpoint Inhibitorsmentioning

confidence: 99%

“…Different mechanisms of weak immunogenicity of DCs have been reported, including failure to induce leukemia-specific CTLs [ 49 ], failure to activate NK cells or γδ T cells [ 65 , 169 , 170 ], failure to overcome the immunosuppressive action of Tregs and MDSCs [ 171 ], and undesired immune effects from Tregs and MDSCs [ 172 ]. Therefore, novel strategies, including DC vaccines combined with HMAs [ 146 ], NK cell infusion or immune checkpoint blockade therapy in relapsed/refractory AML and high-risk MDS patients need to be further validated.…”

Section: Challenges Of DC Vaccinesmentioning

confidence: 99%

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Research progress on dendritic cell vaccines in cancer immunotherapy

et al. 2022

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Dendritic cell (DC) vaccines induce specific immune responses that can selectively eliminate target cells. In recent years, many studies have been conducted to explore DC vaccination in the treatment of hematological malignancies, including acute myeloid leukemia and myelodysplastic syndromes, as well as other nonleukemia malignancies. There are at least two different strategies that use DCs to promote antitumor immunity: in situ vaccination and canonical vaccination. Monocyte-derived DCs (mo-DCs) and leukemia-derived DCs (DCleu) are the main types of DCs used in vaccines for AML and MDS thus far. Different cancer-related molecules such as peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates and DCs/DCleu containing a vaster antigenic repertoire with RNA electroporation, have been used as antigen sources to load DCs. To enhance DC vaccine efficacy, new strategies, such as combination with conventional chemotherapy, monospecific/bispecific antibodies and immune checkpoint-targeting therapies, have been explored. After a decade of trials and tribulations, much progress has been made and much promise has emerged in the field. In this review we summarize the recent advances in DC vaccine immunotherapy for AML/MDS as well as other nonleukemia malignancies.

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Section: Enhancing DC Vaccine Efficacy Via Coadministration With Chemotherapy and Checkpoint Inhibitorsmentioning

confidence: 99%

Section: Enhancing DC Vaccine Efficacy Via Coadministration With Chemotherapy and Checkpoint Inhibitorsmentioning

confidence: 99%

Section: Challenges Of DC Vaccinesmentioning

confidence: 99%

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Research progress on dendritic cell vaccines in cancer immunotherapy

et al. 2022

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“…Furthermore, NY-ESO-1 expressing myeloid cells were demonstrated to elicit a cytotoxic response from autologous NY-ESO-1-specific patient T-cells [ 131 ]. Further investigations combining NY-ESO-1 directed immune responses with hypomethylating agents are ongoing [ 142 ].…”

Section: Cellular and Vaccine Therapies For Mds And Amlmentioning

confidence: 99%

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia

Kapoor

Champion

Basu

et al. 2021

Cancers

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Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most suitable for this treatment remains unclear. Over the past decade, there has been remarkable progress in identifying genomic features of MDS and AML, which has led to an improved discernment of the molecular pathogenesis of these diseases. An improved understanding of immune and inflammatory molecular mechanisms of MDS and AML have also recently revealed novel therapeutic targets. Emerging treatments for MDS and AML include monoclonal antibodies such as immune checkpoint inhibitors, bispecific T-cell-engaging antibodies, antibody drug conjugates, vaccine therapies, and cellular therapeutics including chimeric antigen receptor T-cells and NK cells. In this review, we provide an overview of the current understanding of immune dysregulation in MDS and AML and an update on novel immune therapies for these bone marrow malignancies.

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“…Cancer/testis (CT) antigens (e.g., NY-ESO-1 and SP17), a group of tumor antigens with normal expression restricted to male germ cells and pathological expression in malignant plasma cells, are frequently used and tested in diverse clinical trials with different designs of vaccines [45]. Interestingly, hypomethylating agents routinely used in hematological praxis have the capacity to increase the expression of CT antigens and their combination with vaccination against these antigens might be beneficial [46]. Vaccines against normal peptides preferentially expressed by MM cells represent another approach.…”

Section: Vaccination Strategiesmentioning

confidence: 99%

Harnessing the Immune System to Fight Multiple Myeloma

Krejcik

Barnkob

Nyvold

et al. 2021

Cancers

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Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects.

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Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Cited by 27 publications

References 155 publications

Research progress on dendritic cell vaccines in cancer immunotherapy

Research progress on dendritic cell vaccines in cancer immunotherapy

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia

Harnessing the Immune System to Fight Multiple Myeloma

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