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Author

Hongbo Wang

Other affiliations: Kanazawa University
Bio: Hongbo Wang is an academic researcher from University of Minnesota. The author has contributed to research in topics: Aplastic anemia & Transplantation. The author has an hindex of 12, co-authored 22 publications receiving 730 citations. Previous affiliations of Hongbo Wang include Kanazawa University.

Papers
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Journal ArticleDOI
01 Dec 2002-Blood
TL;DR: The presence of a minor population of P NH-type cells suggests a benign type of bone marrow failure, probably caused by an immunologic mechanism, and peripheral blood should be tested using sensitive flow cytometry for the presence of PNH- type cells in all patients withBone marrow failure before treatment.

201 citations

Journal ArticleDOI
01 Sep 2007-Blood
TL;DR: Collectively, these studies show that CSA influences NK-cell function and phenotype, which may have important implications for graft-versus-leukemia effects.

125 citations

Journal ArticleDOI
TL;DR: iNK cells represent an “off-the-shelf” source of cells for immunotherapy with the capacity to target tumors and engage the adaptive arm of the immune system to make a “cold” tumor “hot” by promoting the influx of activated T cells to augment checkpoint inhibitor therapies.
Abstract: The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors, such as programmed cell death 1 (PD-1), or their ligands, such as PD-L1, has transformed the oncology landscape. However, durable tumor regression is limited to a minority of patients. Therefore, combining immunotherapies with those targeting checkpoint inhibitory receptors is a promising strategy to bolster antitumor responses and improve response rates. Natural killer (NK) cells have the potential to augment checkpoint inhibition therapies, such as PD-L1/PD-1 blockade, because NK cells mediate both direct tumor lysis and T cell activation and recruitment. However, sourcing donor-derived NK cells for adoptive cell therapy has been limited by both cell number and quality. Thus, we developed a robust and efficient manufacturing system for the differentiation and expansion of high-quality NK cells derived from induced pluripotent stem cells (iPSCs). iPSC-derived NK (iNK) cells produced inflammatory cytokines and exerted strong cytotoxicity against an array of hematologic and solid tumors. Furthermore, we showed that iNK cells recruit T cells and cooperate with T cells and anti-PD-1 antibody, further enhancing inflammatory cytokine production and tumor lysis. Because the iNK cell derivation process uses a renewable starting material and enables the manufacturing of large numbers of doses from a single manufacture, iNK cells represent an "off-the-shelf" source of cells for immunotherapy with the capacity to target tumors and engage the adaptive arm of the immune system to make a "cold" tumor "hot" by promoting the influx of activated T cells to augment checkpoint inhibitor therapies.

106 citations

Journal ArticleDOI
TL;DR: It is suggested that a relative increase in the number of PNH granulocytes is a common feature of AA at diagnosis, and that it may represent the presence of immunologic pressure to normal haematopoietic stem cells as a cause of AA.
Abstract: To clarify the pathologic significance of granulocytes exhibiting the paroxysmal nocturnal haemoglobinuria (PNH) phenotype in patients with aplastic anaemia (AA), we examined peripheral blood from 100 patients with AA for the presence of granulocytes deficient in glycosylphosphatidylinositol (GPI)-anchored proteins using a sensitive flow cytometric assay. A significant increase in the frequency of CD55 + CD59 + CD11b + granulocytes (>0.003%) compared to normal individuals was observed in 31 of 35 (88.6%) patients with untreated AA at diagnosis. The proportions of patients showing increased PNH granulocytes in treated AA patients with a short ( 5 yr) disease duration were 68.6% (11/16) and 20.4% (10/49), respectively. When 19 patients showing increased frequency of PNH granulocytes before therapy were studied 6-12 months after antithymocyte globulin plus cyclosporin A therapy, the frequency decreased to 0.01-90% of pretreatment values in 15 recovering patients. These findings suggest that a relative increase in the number of PNH granulocytes is a common feature of AA at diagnosis, and that it may represent the presence of immunologic pressure to normal haematopoietic stem cells as a cause of AA.

63 citations

Journal ArticleDOI
TL;DR: In this article, a triple-gene-edited induced pluripotent stem cell (iPSC) line was generated to express a high affinity, non-cleavable version of the Fc receptor CD16a and a membrane bound interleukin (IL)-15/IL-15R fusion protein.

53 citations


Cited by
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Journal ArticleDOI
Phuong L. Nguyen1
TL;DR: The epidemiology and clinical and pathologic features of MDS and pertinent diagnostic and prognostic classifications are discussed, with a brief overview of treatment options.
Abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders that affect mostly the elderly and have a variable probability of progression to acute leukemia. The diagnosis of MDS rests largely on a critical morphologic review of blood and bone marrow slides, with careful correlation with other clinical and essential laboratory data, including cytogenetics. This article discusses the epidemiology and clinical and pathologic features of MDS and pertinent diagnostic and prognostic classifications, with a brief overview of treatment options. Other considerations in the differential diagnosis are also briefly outlined.

1,103 citations

Journal ArticleDOI
15 Oct 2006-Blood
TL;DR: The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways.

748 citations

Journal ArticleDOI
TL;DR: The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.
Abstract: Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.

729 citations

Journal ArticleDOI
01 Dec 2005-Blood
TL;DR: The primary clinical manifestations of paroxysmal nocturnal hemoglobinuria are hemolytic anemia, marrow failure, and thrombophilia.

673 citations

Journal ArticleDOI
TL;DR: The preferential expansion of a unique subset of NK cells coexpressing the activating CD94–NKG2C receptor and CD57 in CMV+ donors is demonstrated and it is proposed that CD57 might provide a marker of “memory” NK cells that have been expanded in response to infection.
Abstract: During human CMV infection, there is a preferential expansion of natural killer (NK) cells expressing the activating CD94–NKG2C receptor complex, implicating this receptor in the recognition of CMV-infected cells. We hypothesized that NK cells expanded in response to pathogens will be marked by expression of CD57, a carbohydrate antigen expressed on highly mature cells within the CD56dimCD16+ NK cell compartment. Here we demonstrate the preferential expansion of a unique subset of NK cells coexpressing the activating CD94–NKG2C receptor and CD57 in CMV+ donors. These CD57+NKG2Chi NK cells degranulated in response to stimulation through their NKG2C receptor. Furthermore, CD57+NKG2Chi NK cells preferentially lack expression of the inhibitory NKG2A receptor and the inhibitory KIR3DL1 receptor in individuals expressing its HLA-Bw4 ligand. Moreover, in solid-organ transplant recipients with active CMV infection, the percentage of CD57+NKG2Chi NK cells in the total NK cell population preferentially increased. During acute CMV infection, the NKG2C+ NK cells proliferated, became NKG2Chi, and finally acquired CD57. Thus, we propose that CD57 might provide a marker of “memory” NK cells that have been expanded in response to infection.

657 citations