New approaches in the immunotherapy of haematological malignancies

Costello, Régis T.; Rey, Jérôme; Fauriat, Cyril; Gastaut, J A; Olive, Daniel

doi:10.1034/j.1600-0609.2003.00065.x

Cited by 24 publications

(9 citation statements)

References 71 publications

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“…Based on recent clinical and experimental data, NK cells seem to play a crucial role in eradication of acute myeloid leukemia; in contrast, ALL often display a high degree of resistance, the mechanisms of which have not been fully elucidated (30). Thus, the requirement for NK cells in the antileukemia response of MBD2 in our murine model of ALL may be of interest.…”

Section: Discussionmentioning

confidence: 99%

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

et al. 2006

Cancer Research

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Murine B-defensin 2 (MBD2) is a small antimicrobial peptide of the innate immune system. Recent study showed that MBD2 could not only recruit immature dendritic cells but also activate them by Toll-like receptor 4 and thus may provide a critical link between the innate immune system and the adaptive immune response. In this report, we examined the antileukemia activity of MBD2 in a murine model of acute lymphoid leukemia (ALL) L1210. L1210 cells were engineered to secrete biologically functional MBD2. MBD2-modified L1210 (L1210-MBD2) showed significantly reduced leukemogenecity, resulting in a 80% rate of complete leukemia rejection. Inoculation of mice with L1210-MBD2 induced enhanced CTL and natural killer (NK) activity and augmented interleukin-12 and IFN-; production. All the recovered mice from the inoculation showed a protective immunity to the following challenge with parental L1210 cells and generate leukemia-specific memory CTL. Vaccines with irradiated L1210-MBD2 cells could cure 50% leukemia-bearing mice. Depletion of CD8 + T cells but not CD4 + T cells completely abrogated the antileukemia activity of MBD2. Interestingly, NK cells were also required for the MBD2-mediated antileukemia response, although ALL generally display a high degree of resistance to NK-mediated lysis. Our results suggest that MBD2 can activate both innate and adaptive immunity to generate potent antileukemia response, and MBD2 immunotherapy warrants further evaluation as a potential treatment for ALL. (Cancer Res 2006; 66(2): 1169-76)

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Section: Discussionmentioning

confidence: 99%

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

et al. 2006

Cancer Research

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“…Therefore further studies are needed in order to better understand the disease and to improve the patient outcome. T cell immunodeficiency was suggested to play an important role in tumor progression, facilitating the expansion of the malignant clone [2,3], although the interaction between the tumor and the immune system is still not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Decreased level of recent thymic emigrants in CD4+ and CD8+T cells from CML patients

Geng

Yin

et al. 2010

J Transl Med

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BackgroundT-cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor. Based on our previous finding, to further characterize the immune status, T cell proliferative history was analyzed in CD4+ and CD8+ T cells from chronic myeloid leukemia (CML) patients.MethodsQuantitative analysis of δRec-ψJα signal joint T cell receptor excision circles (sjTRECs) was performed in PBMCs, CD3+, CD4+ and CD8+T cells by real-time PCR, and the analysis of 23 TRBV-D1 sjTRECs was performed by semi-nested PCR. Forty eight CML cases in chronic phase (CML-CP) were selected for this study and 17 healthy individuals served as controls.ResultsThe levels of δRec-ψJα sjTRECs in PBMCs, CD3+, CD4+, and CD8+ T cells were significantly decreased in CML patients, compared with control groups. Moreover, the numbers of detectable TRBV subfamily sjTRECs, as well as the frequency of particular TRBV-BD1 sjTRECs in patients with CML were significantly lower than those from healthy individuals.ConclusionsWe observed decreased levels of recent thymic emigrants in CD4+ and CD8+ T cells that may underlay the persistent immunodeficiency in CML patients.

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“…The insufficient expression/presentation of costimulatory antigens, major histocomaptibility complex (MHC) molecules and tumor-associated peptides/antigens on the surface of cancer cells and disturbed mechanisms of apoptosis are the main reasons for an ineffective immune response in oncologic diseases. 4 As professional antigen presenting cells (APCs) dendritic cells (DC) specifically stimulate the development of T-effector cells, especially tumor-cytotoxic T cells. Therefore they are regarded as interesting candidates for antitumor or antileukemic vaccination strategies.…”

mentioning

confidence: 99%

Dendritic Cells (DCs) Can Be Successfully Generated From Leukemic Blasts in Individual Patients With AML or MDS

Kremser¹,

Dressig²,

Grabrucker³

et al. 2010

Journal of Immunotherapy

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Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

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New approaches in the immunotherapy of haematological malignancies

Cited by 24 publications

References 71 publications

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

Vaccine with β-Defensin 2–Transduced Leukemic Cells Activates Innate and Adaptive Immunity to Elicit Potent Antileukemia Responses

Decreased level of recent thymic emigrants in CD4+ and CD8+T cells from CML patients

Dendritic Cells (DCs) Can Be Successfully Generated From Leukemic Blasts in Individual Patients With AML or MDS

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