Abstract:
:Interleukin (IL)-2 therapy given at tolerable doses is insufficient to induce maximum activation of natural killer (NK) cells. We recently demonstrated that NK cells expanded in vivo can be maximally activated by short-term ex vivo incubation with 1000 U/mL IL-2. However, IL-2 withdrawal, which would occur with reinfusion, may lead to a rapid loss of cell viability and function. We hypothesized that retroviral transduction could provide an endogenous source of IL-2 to maintain NK function as measured by proliferation and cytotoxicity. Enriched NK cells were transduced with supernatants containing an MFG-based retrovirus designed to express murine IL-2 cDNA. Several supernatant transduction strategies were evaluated. NK cells were initially cultured in 1000 U/mL of huIL2 for 7-8 days, harvested, and replated prior to transduction (4 hours at 37degrees C); this proved insufficient to sustain NK proliferation or maintain cytotoxicity after exogenous human IL-2 (huIL-2) withdrawal. An alternative transduction procedure using phosphate-depleted medium, centrifugation, and transduction for 16 hours at 32degrees C was then evaluated. NK cells transduced under these conditions maintained significant NK proliferation in the absence of exogenous IL-2 compared with sham-transduced controls. Two consecutive daily transductions resulted in less proliferation, suggesting that several exposures to retroviral supernatant may inhibit subsequent NK proliferation. Cytotoxicity of the transduced NK cells against K562 and Raji was maintained under these conditions without exogenous IL-2. Sham-transduced NK cells produced 8.3+/-2.6 U/mL of murine IL-2 (muIL-2) by ELISA (background) after 7 days without exogenous IL-2. In contrast, 109+/-23 U/mL muIL-2 was produced by NK cells transduced with supernatant from the MFG/muIL-2 producer line. These experiments demonstrate that NK cells can be successfully transduced with retroviruses and induced to express sufficient IL-2 to maintain their proliferative and cytotoxic functions. Transduction of IL-2 genes into NK cells may offer advantages over exogenous IL-2 administration in maintaining maximum function for use in antitumor immunotherapy.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Miller JS,Tessmer-Tuck J,Blake N,Lund J,Scott A,Blazar BR,Orchard PJsubject
Has Abstractpub_date
1997-10-01 00:00:00pages
1140-8issue
11eissn
0301-472Xissn
1873-2399journal_volume
25pub_type
杂志文章abstract::The course of development of graft-versus-host reactions (GVHR) following lethal irradiation was compared in two mouse donor-host combinations disparate at non H-2 loci alone or associated to H-2 complex. The pathogenesis of these reactions was very different (mortality rates faster in the second situation for example...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-05-01 00:00:00
abstract::Hematopoietic progenitor cells (low density, lineage negative [Lin-], depleted of CD4+, CD8+, B220+, Gr-1+, Mac-1+, CD71+, and Thy1.2+ cells) can engraft lethally irradiated mice when transplanted within, but not across the major histocompatibility (MHC) antigen barrier. We hypothesized that our progenitor cell prepar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained rem...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.04.022
更新日期:2006-09-01 00:00:00
abstract::Lifelong blood production is ensured by a population of rare and largely quiescent, long-lived hematopoietic stem cells (HSCs). The advent of single-cell technologies has recently highlighted underlying molecular and functional heterogeneity within the HSC pool. Despite heterogenous HSC behaviors, quiescence remains a...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.11.003
更新日期:2020-12-01 00:00:00
abstract::The effect of partially purified thrombopoietic stimulatory factor (TSF) on megakaryocytopoiesis was studied using the soft-gel colony-forming assay and a short-term marrow liquid culture system (STLC) and compared to the effects of megakaryocyte colony-stimulating activity present in pokeweed mitogen-stimulated splee...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::The bcr/abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia (CML). The Haseloff and Gerlach model was used to design a ribozyme targeted to this transcript. When tested against a synthetic substrate covering the translocation sequence, the ribozyme exhibited si...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract:OBJECTIVE:We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning. METHODS:Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-flud...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00201-7
更新日期:2003-10-01 00:00:00
abstract::The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The co...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract::An improved negative immunomagnetic selection strategy has been devised for the enrichment of primitive hemopoietic cells using the high proliferative potential colony-forming cell (HPP-CFC) assay as an index of stem cell purification. Immunomagnetic selection was carried out using goat anti-rat conjugated M-450 Dynab...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therap...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.10.001
更新日期:2019-11-01 00:00:00
abstract::Mammalian tissue culture cells when cryopreserved according to standard procedures do not show gross chromosomal changes as evidenced by the formation of micronuclei. Cryoprotective agents used in this study included dimethyl sulfoxide (DMSO), glycerol and polyvinylpyrollidone (PVP) in combination with serum and using...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
abstract::Nasal natural killer-T cell lymphoma (NNKTL) is associated with the Epstein-Barr virus and has distinct histologic features, such as angiocentric and polymorphous lymphoreticular infiltrates that contain too many cell types, including tumor and inflammatory cells. We have shown previously that intercellular adhesion m...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2013.03.009
更新日期:2013-08-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development. MATERIALS AND METHODS:Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00128-9
更新日期:2000-01-01 00:00:00
abstract::The first blood cells observed in the embryo are large nucleated erythroblasts generated in blood islands of the extraembryonic yolk sac. These unique red cells have been termed primitive because of their resemblance to nucleated erythroblasts of nonmammalian species. It is now widely assumed that hematopoiesis in the...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2005.06.012
更新日期:2005-09-01 00:00:00
abstract:OBJECTIVE:A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS:The HSC activity of porcine c-kit+ BMCs was ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00197-8
更新日期:2003-09-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 00:00:00
abstract::Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:OBJECTIVE:Adenoviral vectors (Ad) were widely used in gene therapy and study of gene function, but the commonly used serotype 5 adenovirus-based vectors (Ad5) could poorly transduce hematopoietic cells because of low expression of viral receptors on these cells. To overcome this limitation, we developed a retargeting a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.005
更新日期:2006-09-01 00:00:00
abstract:OBJECTIVE:Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.001
更新日期:2010-11-01 00:00:00
abstract::High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in the treatment of malignancies is often associated with immune deficiency following transplantation, possibly contributing to tumor relapse or fatal infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex (MHC)-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::The effect on marrow myeloblast colony formation in blood from nine patients with acute myeloid leukemia was studied by using three recombinant-DNA-derived human leukocyte interferons (IFN alpha 2, IFN alpha-A, and IFN alpha-C). In preliminary experiments, a brief exposure of leukemic marrow cells to IFN alpha resulte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Discontinuous albumin density gradients were used to physically separate hemopoietic cells from immunocompetent lymphocytes in peripheral blood mononuclear cells of dogs. Transplantation of these stem cell concentrates into lethally irradiated allogeneic recipients restored hemopoiesis in nine of 12 animals. Tolerance...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Hematopoietic stem/progenitor cells (HSPCs) play important roles in fighting systemic infection as they supply immune cells in a demand-adapted manner. Various mechanisms govern HSPC responses to infection, including cytokine signaling, niche function, and direct sensing of pathogen-derived molecules by HSPCs themselv...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.11.008
更新日期:2016-02-01 00:00:00
abstract::The transcription factor RUNX1 is required in the embryo for formation of the adult hematopoietic system. Here, we describe the seminal findings that led to the discovery of RUNX1 and of its critical role in blood cell formation in the embryo from hemogenic endothelium (HE). We also present RNA-sequencing data demonst...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.10.009
更新日期:2018-12-01 00:00:00
abstract::Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract:OBJECTIVE:Recent clinical trials of adoptive immunotherapy showed diminished reactivity of human T cells upon ex vivo manipulation. For a safe and effective clinical application of human T cells, it is necessary to improve ex vivo manipulation procedures and evaluate their impact on in vivo functionality. However, ther...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.09.018
更新日期:2007-01-01 00:00:00
abstract::We detail a novel, sensitive, and reproducible in vitro bioassay for erythropoietin that can be performed conveniently in any laboratory and is well suited for analysis of large numbers of samples. The assay measures DNA synthesis by a cohort of highly erythropoietin-responsive red cell precursors appearing in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00