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Immunotherapy versus Immune Modulation of Leukemia
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Immunotherapy versus Immune Modulation of Leukemia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 1290

Special Issue Editor

Prof. Dr. Helga Maria Schmetzer

E-Mail Website
Guest Editor
Med III, Department for Hematopoetic Transplantations, Klinikum Grosshadern, Ludwig-Maximilian-University of Munich, Marchioninistrße 15, 81377 Munich, Germany
Interests: dendritic cells; leukemia derived DC; AML; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most patients with acute myeloid leukemia (AML) initially respond to chemotherapy; however, 80% of patients relapse soon after due to reoccurring blasts.

Besides allogeneic standard stem cell transplantation antibodies (e.g targeting checkpoint molecules) and cellular CAR-T or -NK, cell immunotherapeutic strategies aim to overcome the problem of the few available neoantigens in AML. Extracellular vesicles (carrying signaling molecules or RNA cargo) are being tested for antileukemic activity. In addition, pharmacological immune modulating strategies influencing cell proliferation, apoptosis, and signal transducing pathways are being tested to overcome drug resistance and sensitize blasts to chemotherapy.

Engineered or leukemia-derived dendritic cells (DCs/DCleu) link the adaptive and innate immunity and mediate blast killing ex vivo and in vivo. Drug-induced DCleu from blasts in vivo could stabilize remissions or the disease in AML patients via induced immune modulation

Here, we summarize immunotherapies that are needed to destroy leukemic cells and (immune) modulating strategies to change the cellular/soluble microenvironment into an “antileukemic environment” stabilize antileukemic processes, and overcome resistance.

Prof. Dr. Helga Maria Schmetzer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • leukemia
  • immunotherapy
  • immune modulation
  • antileukemic
  • drug resistance

Published Papers (1 paper)

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Research

26 pages, 3699 KiB  
Article
Granulocyte-Macrophage-Colony-Stimulating-Factor Combined with Prostaglandin E1 Create Dendritic Cells of Leukemic Origin from AML Patients’ Whole Blood and Whole Bone Marrow That Mediate Antileukemic Processes after Mixed Lymphocyte Culture
by Marianne Unterfrauner, Hazal Aslan Rejeski, Anne Hartz, Sophia Bohlscheid, Tobias Baudrexler, Xiaojia Feng, Elias Rackl, Lin Li, Andreas Rank, Giuliano Filippini Velázquez, Christoph Schmid, Jörg Schmohl, Peter Bojko and Helga Schmetzer
Int. J. Mol. Sci. 2023, 24(24), 17436; https://doi.org/10.3390/ijms242417436 - 13 Dec 2023
Viewed by 1071
Abstract
Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) [...] Read more.
Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) converts myeloid blasts into dendritic cells of leukemic origin (DCleu). After stimulation with DCleu ex vivo, leukemia-specific antileukemic immune cells are activated. Therefore, Kit-M treatment may be an attractive immunotherapeutic tool to treat patients with myeloid leukemia. Kit-M-mediated antileukemic effects on whole bone marrow (WBM) were evaluated and compared to whole blood (WB) to evaluate the potential effects of Kit-M on both compartments. WB and WBM samples from 17 AML patients at first diagnosis, in persisting disease and at relapse after allogeneic stem cell transplantation (SCT) were treated in parallel with Kit-M to generate DC/DCleu. Untreated samples served as controls. After a mixed lymphocyte culture enriched with patients’ T cells (MLC), the leukemia-specific antileukemic effects were assessed through the degranulation- (CD107a+ T cells), the intracellular IFNγ production- and the cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flow cytometry. In both WB and WBM significantly higher frequencies of (mature) DCleu were generated without induction of blast proliferation in Kit-M-treated samples compared to control. After MLC with Kit-M-treated vs. not pretreated WB or WBM, frequencies of (leukemia-specific) immunoreactive cells (e.g., non-naive, effector-, memory-, CD3+β7+ T cells, NK- cells) were (significantly) increased, whereas leukemia-specific regulatory T cells (Treg, CD152+ T cells) were (significantly) decreased. The cytotoxicity fluorolysis assay showed a significantly improved blast lysis in Kit-M-treated WB and WBM compared to control. A parallel comparison of WB and WBM samples revealed no significant differences in frequencies of DCleu, (leukemia-specific) immunoreactive cells and achieved antileukemic processes. Kit-M was shown to have comparable effects on WB and WBM samples regarding the generation of DCleu and activation of (antileukemic) immune cells after MLC. This was true for samples before or after SCT. In summary, a potential Kit-M in vivo treatment could lead to antileukemic effects in WB as well as WBM in vivo and to stabilization of the disease or remission in patients before or after SCT. A clinical trial is currently being planned. Full article
(This article belongs to the Special Issue Immunotherapy versus Immune Modulation of Leukemia)
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