Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1)

Abdul-Hai, Ali; Weiss, Lola; Ben‐Yehuda, Arie; Ergas, David; Shapira, M Y; Slavin, Shimon

doi:10.1038/sj.bmt.1705819

Cited by 8 publications

(4 citation statements)

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“…This assumption was indeed proven in a BCL-1 B-cell leukemia mouse model [53] where the efficacy of nSSL-MPS was compared to non-encapsulated free-MPS. The BCL-1 cell line [53] is characterized by its high sensitivity to GCs, having an in vitro growth inhibition (GI 50 ) in the nanomolar range (∼4.2 nM).…”

Section: Resultsmentioning

confidence: 81%

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Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

et al. 2011

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We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies.

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Section: Resultsmentioning

confidence: 81%

“…The BCL-1 cell line [53] is characterized by its high sensitivity to GCs, having an in vitro growth inhibition (GI 50 ) in the nanomolar range (∼4.2 nM).…”

Section: Resultsmentioning

confidence: 99%

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Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

et al. 2011

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“…Several studies in murine bone marrow transplantation models have documented that post‐transplant IL‐7 administration to recipients of syngeneic or allogeneic bone marrow transplantation enhances lymphoid reconstitution 13–15. Moreover, IL‐7 increased homeostatic proliferation of transferred and de novo generated T cells 16.…”

Section: Introductionmentioning

confidence: 99%

Chronic myelogenous leukemia maintains specific CD8⁺ T cells through IL‐7 signaling

et al. 2010

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Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease of hematopoietic stem cells. The disease progresses after several years from an initial chronic phase to a blast phase. Leukemia-specific T cells are regularly detected in CML patients and may be involved in the immunological control of the disease. Here, we analyzed the role of leukemia-specific CD81 T cells in CML disease control and the mechanism that maintains CD8 1 T-cell immunosurveillance in a retroviral-induced murine CML model. To study antigen-specific immune responses, the glycoprotein of the lymphocytic choriomeningitis virus was used as model leukemia antigen. Leukemiaspecific CTL activity was detectable in vivo in CML mice and depletion of CD8 1 T cells rapidly led to disease progression. CML-specific CTL were characterized by the expression of the IL-7 receptor a-chain. In addition, leukemia cells produced IL-7 that was crucial for the maintenance of leukemia-specific CTL and for disease control. Therefore, CML cells maintain the specific CD8 1 T-cell-mediated immune control by IL-7 secretion. This results in prolonged control of disease and probably contributes to the characteristic chronic phase of the disease.Key words: CD8 1 T cells . Chronic myelogenous leukemia . IL-7 signaling Supporting Information available online IntroductionChronic myelogenous leukemia (CML) is a malignant clonal disease originating from a pluripotent hematopoietic stem cell expressing the reciprocal translocation t(9;22), which forms the oncogenic BCR/ABL fusion protein. BCR/ABL is a constitutively activated tyrosine kinase which plays a critical role in the pathogenesis of CML. After several years and acquisition of a second genetic abnormality, the disease progresses from the chronic phase to terminal blast phase in which the patients develop an acute leukemia of either myeloid (AML) or, less frequent, lymphoid (ALL) cell type [1][2][3]. For unknown reasons, CML seems to be the most immunogenic leukemia. Experiences from stem cell transplantations (SCT) suggest that T cells play an important role in the immunological control of CML. After allogeneic SCT, recipients of T-cell-depleted grafts have a higher incidence of relapses, and post-transplant relapses can be restored to permanent molecular remissions by donor lymphocyte infusions [4,5]. In addition, specific CTL recognizing leukemia antigens such as BCR/ABL, proteinase-3 and Wilms tumor 1 protein have been identified in CML patients without SCT [6]. However, in the peripheral blood Ã These authors have contributed equally to this work. 2720of CML patients, only low-avidity CTL were detectable. Highavidity CTL might have been deleted through apoptotic processes due to the persistence of the CML [7]. Nevertheless, CML-specific CTL may be involved in the control of the leukemia in the chronic phase over several years and coexist with the leukemia. The mechanisms controlling this delicate balance between the immune system and leukemia are largely unknown. CD8 1 T cells are activated and dev...

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Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies

et al. 2011

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* b b-thalassemias are characterized by an imbalance of globin chains with an excess of a-chains which precipitates in erythroid precursors and red blood cells (RBCs) leading to inefficient erythropoiesis. The severity of the disease correlates with the amount of unpaired achains. Our goal was to develop a simple test for evaluation of the free a-hemoglobin pool present in RBC lysates. Alpha-Hemoglobin Stabilizing Protein (AHSP), the chaperone of a-Hb, was used to trap excess aHb. A recombinant GST-AHSP fusion protein was bound to an affinity micro-column and then incubated with hemolysates of patients. After washing, the a-Hb was quantified by spectrophotometry in the elution fraction. This assay was applied to 54 patients: 28 without apparent Hb disorder, 20 b-thalassemic and 6 a-thalassemic. The average value of free a-Hb pool was 93 ± 21 ppm (ng of free a-Hb per mg of Hb subunits) in patients without Hb disorder, while it varies from 119 to 1,756 ppm, in b-thalassemic patients and correlated with genotype. In contrast, the value of the free a-Hb pool was decreased in a-thalassemic patients (65 ± 26 ppm). This assay may help to characterize b-thalassemia phenotypes and to follow the evolution of the globin chain imbalance (a/b+c ratio) in response to treatment.b-thalassemias (b-thal) are inherited autosomal diseases characterized by a decreased or abolished b-globin chain biosynthesis [1]. During the transition of g to b globin expression in the first year of life, the clinical severity is mainly related to the ratio a/b1g which indicates the level of chain disequilibrium. b-thal are generally classified as minor, intermediate, or major phenotype, and encompass a wide clinical spectrum ranging from asymptomatic carriers to forms that can be lethal in the absence of extensive treatment. Different factors can modulate the severity of this disease [2] such as the magnitude of the decrease of the b globin synthesis, for example hemoglobin E (Hb E b26Glu?Lys) [3], or with the co-inheritance of (i) an a-thalassemia (a-thal) [4], (ii) a triplicated a-globin gene [5] or (iii) a low but variable residual capacity of g globin production which can have the phenotype of a hereditary persistence of fetal Hb (Hb F a 2 g 2 ) [6].The imbalance between a and non a-globin (g1d1b) synthesis was established by radioactive in vitro biosynthesis of globin chains from reticulocytes or of bone marrow of b-thalassemic patients [7][8][9][10]. This imbalance leads to an excess of highly unstable free a-hemoglobin (a-Hb), precipitating on the cell membrane and acting as active oxidants causing apoptosis and inefficient erythropoiesis [1,11]. The severity of b-thal is directly correlated with the degree of imbalance as quantified by the amount of unbound a-globin chain [12]. Many studies have shown that one observes a soluble a chain fraction present in the cytosolic RBC and an insoluble a chain fraction in the membrane of b-thalassemic erythrocytes [13,14]. Because of technical difficulties and the burden of using radioactive materials...

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Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1)

Cited by 8 publications

References 17 publications

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

Chronic myelogenous leukemia maintains specific CD8⁺ T cells through IL‐7 signaling

Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies

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Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1)

Cited by 8 publications

References 17 publications

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

Chronic myelogenous leukemia maintains specific CD8+ T cells through IL‐7 signaling

Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies

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Chronic myelogenous leukemia maintains specific CD8⁺ T cells through IL‐7 signaling