Combined immunophenotyping and fluorescence<i>in situ</i>hybridization with chromosome-specific DNA probes allows quantification and differentiation of<i>ex vivo</i>generated dendritic cells, leukemia-derived dendritic cells and clonal leukemic cells in patients with acute myeloid leukemia

Kremser, Andreas; Kufner, Stefanie; Konhaeuser, Elke; Kroell, Tanja; Hausmann, Andreas; Tischer, Johanna; Kolb, Hans‐Jochem; Zitzelsberger, Horst; Schmetzer, Helga

doi:10.3109/10428194.2012.751490

Cited by 8 publications

(8 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, we and others could already show that clonal leukemic blasts can be regularly converted to DC leu with different DC/DC leu -generating protocols, independent from age, FAB-classification, mutation or hematopoietic stem cell transplantation (HSCT) status, mutations of the disease, and FAB classification [17,51]. The clonal leukemic origin of DC leu was already confirmed with fluorescence in situ hybridization (FISH) analysis [52].…”

Section: Discussionmentioning

confidence: 97%

PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood

Amberger

Doraneh-Gard

Gunsilius

et al. 2019

IJMS

View full text Add to dashboard Cite

Dendritic cells (DCs) and leukemia-derived DC (DCleu) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the immune system. As a potential treatment tool for patients with acute myeloid leukemia, we developed and analyzed two new PGE1-containing protocols (Pici-PGE1, Kit M) to generate DC/DCleu ex vivo from leukemic peripheral blood mononuclear cells (PBMCs) or directly from leukemic whole blood (WB) to simulate physiological conditions. Pici-PGE1 generated significantly higher amounts of DCs from leukemic and healthy PBMCs when compared to control and comparable amounts as the already established protocol Pici-PGE2. The proportions of sufficient DC-generation were even higher after DC/DCleu-generation with Pici-PGE1. With Kits, it was possible to generate DCs and DCleu directly from leukemic and healthy WB without induction of blast proliferation. The average amounts of generated DCs and DCleu-subgroups were comparable with all Kits. The PGE1 containing Kit M generated significantly higher amounts of mature DCs when compared to the PGE2-containing Kit K and increased the anti-leukemic-activity. In summary PGE1-containing protocols were suitable for generating DC/DCleu from PBMCs as well as from WB, which reliably (re-) activated immunoreactive cells, improved the overall ex vivo anti-leukemic activity, and influenced cytokine-release-profiles.

show abstract

Section: Discussionmentioning

confidence: 97%

PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood

Amberger

Doraneh-Gard

Gunsilius

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…[26][27][28][29][30] Those DCleu can be quantified, for example, by combined fluorescence and in situ cell stainings (using patients' chromosomal aberrations in combination with DC-markers) as already shown. 31 Even better flowcytometric quantifications co-detecting patients' blast markers and the (gained) DCmarkers allow a quantitative and qualitative detection of DC and DCleu, as shown by us. 32 DCleu potentially present the complete leukemic antigenic repertoire of individual patients, without the need of tumor antigen-pulsing.…”

mentioning

confidence: 80%

In Vitro Generated Dendritic Cells of Leukemic Origin Predict Response to Allogeneic Stem Cell Transplantation in Patients With AML and MDS

Freudenreich¹,

Tischer²,

Kroell³

et al. 2021

Journal of Immunotherapy

Self Cite

View full text Add to dashboard Cite

Allogeneic stem cell transplantation (alloSCT) is the treatment of choice for many patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. The presentation of leukemic or allospecific antigens by malignant blasts is regarded as a crucial trigger for an effective allogeneic immune response. Conversely, insufficient stimulatory capacity by the leukemic blasts is thought to be a relevant escape mechanism from cellular immunotherapy (alloSCT). Our purpose was to test, whether the ability of malignant blasts to differentiate in vitro toward dendritic cells of leukemic origin (DCleu) is associated with clinical outcome. We isolated leukemic blasts from peripheral blood or bone marrow of AML and myelodysplastic syndrome patients before alloSCT (n = 47) or at relapse after alloSCT (n = 22). A panel of 6 different assays was used to generate DCleu in vitro. Results were correlated with clinical outcome. DCleu could be generated from all 69 samples. Significantly higher mean frequencies of DCleu were found in clinical long-term responders versus nonresponders to SCT (76.8% vs. 58.8%, P = 0.006). Vice versa, the chance for response to SCT was significantly higher, if a DCleu+/dendritic cells (DC) ratio of > 50% could be reached in vitro (P = 0.004). Those patients were characterized by a longer time to relapse (P = 0.04) and by a higher probability for leukemia-free survival (P = 0.005). In vitro generation of DC and DCleu from leukemic blasts correlated with the clinical outcome. This observation may support a role of leukemic antigen presentation by "leukemia-derived DC" for the stimulation of an allogeneic immune response in AML.

show abstract

“…Analysis of these DCleu demonstrated the expression of various specific whole leukemic antigens from patients [ 31 , 32 ]. The confirmation methods of DCleu include Western blot, immunophenotyping and fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes to detect leukemia-specific numeric or structural chromosomal aberrations in the generated DCleu [ 33 , 34 ]. Additionally, a special flow cytometric gating strategy has been developed.…”

Section: Vaccine Cell Types and Clinical Datamentioning

confidence: 99%

Research progress on dendritic cell vaccines in cancer immunotherapy

Sun

Cao

et al. 2022

Exp Hematol Oncol

View full text Add to dashboard Cite

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.

show abstract

Combined immunophenotyping and fluorescencein situhybridization with chromosome-specific DNA probes allows quantification and differentiation ofex vivogenerated dendritic cells, leukemia-derived dendritic cells and clonal leukemic cells in patients with acute myeloid leukemia

Cited by 8 publications

References 19 publications

PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood

PGE1-Containing Protocols Generate Mature (Leukemia-Derived) Dendritic Cells Directly from Leukemic Whole Blood

In Vitro Generated Dendritic Cells of Leukemic Origin Predict Response to Allogeneic Stem Cell Transplantation in Patients With AML and MDS

Research progress on dendritic cell vaccines in cancer immunotherapy

Contact Info

Product

Resources

About