scholarly journals TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1

Blood ◽  
2017 ◽  
Vol 129 (10) ◽  
pp. 1284-1295 ◽  
Author(s):  
Lorenz Jahn ◽  
Pleun Hombrink ◽  
Renate S. Hagedoorn ◽  
Michel G. D. Kester ◽  
Dirk M. van der Steen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factor ◽  
B Cell ◽  
B Cell Malignancies ◽  
High Affinity ◽  
Isolation And Characterization ◽  
Key Points

Key Points Isolation and characterization of a high-affinity TCR targeting the intracellular B cell–specific transcription factor BOB1. T cells expressing a BOB1-specific TCR lysed and eradicated primary multiple myeloma and other B-cell malignancies in vitro and in vivo.

The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP

1992 ◽  
Vol 12 (6) ◽  
pp. 2662-2672
Author(s):  
Z Kozmik ◽  
S Wang ◽  
P Dörfler ◽  
B Adams ◽  
M Busslinger
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
B Cell ◽  
Lymphoid Cells ◽  
Binding Studies ◽  
Specific Transcription Factor ◽  
High Affinity ◽  
B Lymphoid

The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.

scholarly journals The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP.

1992 ◽  
Vol 12 (6) ◽  
pp. 2662-2672 ◽  
Author(s):  
Z Kozmik ◽  
S Wang ◽  
P Dörfler ◽  
B Adams ◽  
M Busslinger
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
B Cell ◽  
Lymphoid Cells ◽  
Binding Studies ◽  
Specific Transcription Factor ◽  
High Affinity ◽  
B Lymphoid

The CD19 protein is expressed on the surface of all B-lymphoid cells with the exception of terminally differentiated plasma cells and has been implicated as a signal-transducing receptor in the control of proliferation and differentiation. Here we demonstrate complete correlation between the expression pattern of the CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B-lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP-binding sites have been mapped by in vitro protein-DNA binding studies. In particular, a high-affinity BSAP-binding site instead of a TATA sequence is located in the -30 promoter region upstream of a cluster of heterogeneous transcription start sites. Moreover, this site is occupied by BSAP in vivo in a CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity site has been conserved in the promoters of both human and mouse CD19 genes and was furthermore shown to confer B-cell specificity to a beta-globin reporter gene in transient transfection experiments. In addition, BSAP was found to be the only abundant DNA-binding activity of B-cell nuclear extracts that interacts with the CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation of the CD19 gene.

scholarly journals Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies

Blood ◽  
2017 ◽  
Vol 130 (18) ◽  
pp. 2018-2026 ◽  
Author(s):  
Maureen C. Ryan ◽  
Maria Corinna Palanca-Wessels ◽  
Brian Schimpf ◽  
Kristine A. Gordon ◽  
Heather Kostner ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Preclinical Models ◽  
B Cell Malignancies ◽  
Key Points

Key Points SGN-CD19B is broadly active in vitro against malignant B-cell lines, including double-hit and triple-hit lymphoma cell lines. SGN-CD19B shows significant antitumor activity in vivo in preclinical models of B-NHL and B-cell–derived acute lymphoblastic leukemia.

The influential T cell in B-cell neoplasms.

1983 ◽  
Vol 1 (12) ◽  
pp. 810-816 ◽  
Author(s):  
N E Kay ◽  
M M Oken ◽  
R T Perri
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Clinical Effects ◽  
B Cell Malignancies

Investigations of human B-cell malignancies have generally focused on the monoclonal B-cell populations. Until recently there has been little emphasis on the thymus (T) lymphocyte in these disorders. Current studies, however, suggest that quantitative and qualitative disorders of T cells are generally seen both in chronic lymphocytic leukemia and in multiple myeloma. This review will focus on two major concepts. First, it will define the quantitative and functional T-cell abnormalities in B-cell malignancies including evidence suggesting a causal link between the T-cell abnormalities and certain observed disease manifestations in chronic lymphocytic leukemia and multiple myeloma. Secondly, it will review data demonstrating that these T cells may be influenced by in vivo and in vitro manipulations and will outline some of the possible resultant clinical effects.

scholarly journals Isolation and characterization of a gene (CBF2) specifying a protein component of the budding yeast kinetochore.

1993 ◽  
Vol 121 (3) ◽  
pp. 513-519 ◽  
Author(s):  
W Jiang ◽  
J Lechner ◽  
J Carbon
Keyword(s):  
Molecular Motors ◽  
Cell Biology ◽  
Budding Yeast ◽  
Isolation And Characterization ◽  
Sequence Homologies ◽  
Binding Factor ◽  
Microtubule Motor

We have cloned and determined the nucleotide sequence of the gene (CBF2) specifying the large (110 kD) subunit of the 240-kD multisubunit yeast centromere binding factor CBF3, which binds selectively in vitro to yeast centromere DNA and contains a minus end-directed microtubule motor activity. The deduced amino acid sequence of CBF2p shows no sequence homologies with known molecular motors, although a consensus nucleotide binding site is present. The CBF2 gene is essential for viability of yeast and is identical to NDC10, in which a conditional mutation leads to a defect in chromosome segregation (Goh, P.-Y., and J. V. Kilmartin, in this issue of The Journal of Cell Biology). The combined in vitro and in vivo evidence indicate that CBF2p is a key component of the budding yeast kinetochore.

scholarly journals Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress

2018 ◽  
Vol 115 (51) ◽  
pp. 12997-13002 ◽  
Author(s):  
Charlotte Steenblock ◽  
Maria F. Rubin de Celis ◽  
Luis F. Delgadillo Silva ◽  
Verena Pawolski ◽  
Ana Brennand ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Differentiated Cells ◽  
Isolation And Characterization ◽  
Proliferation And Differentiation ◽  
Response To Stress ◽  
Steroidogenic Cells ◽  
High Degree

The adrenal gland is a master regulator of the human body during response to stress. This organ shows constant replacement of senescent cells by newly differentiated cells. A high degree of plasticity is critical to sustain homeostasis under different physiological demands. This is achieved in part through proliferation and differentiation of adult adrenal progenitors. Here, we report the isolation and characterization of a Nestin+ population of adrenocortical progenitors located under the adrenal capsule and scattered throughout the cortex. These cells are interconnected with progenitors in the medulla. In vivo lineage tracing revealed that, under basal conditions, this population is noncommitted and slowly migrates centripetally. Under stress, this migration is greatly enhanced, and the cells differentiate into steroidogenic cells. Nestin+ cells cultured in vitro also show multipotency, as they differentiate into mineralocorticoid and glucocorticoid-producing cells, which can be further influenced by the exposure to Angiotensin II, adrenocorticotropic hormone, and the agonist of luteinizing hormone-releasing hormone, triptorelin. Taken together, Nestin+ cells in the adult adrenal cortex exhibit the features of adrenocortical progenitor cells. Our study provides evidence for a role of Nestin+ cells in organ homeostasis and emphasizes their role under stress. This cell population might be a potential source of cell replacement for the treatment of adrenal insufficiency.

scholarly journals Pharmaceutical properties of 'sucupira' (Pterodon spp.)

2010 ◽  
Vol 46 (4) ◽  
pp. 607-616 ◽  
Author(s):  
Daiane Hansen ◽  
Mitsue Haraguchi ◽  
Antonio Alonso
Keyword(s):  
Biological Effects ◽  
Chemical Compounds ◽  
Experimental Models ◽  
Popular Medicine ◽  
Isolation And Characterization ◽  
Pharmaceutical Properties ◽  
The Relationship

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.

A Drosophila doublesex-related gene, terra, is involved in somitogenesis in vertebrates

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1259-1268 ◽  
Author(s):  
A. Meng ◽  
B. Moore ◽  
H. Tang ◽  
B. Yuan ◽  
S. Lin
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Dna Binding Domain ◽  
Related Gene ◽  
Presomitic Mesoderm ◽  
Zinc Finger Gene ◽  
Human And Mouse

The Drosophila doublesex (dsx) gene encodes a transcription factor that mediates sex determination. We describe the characterization of a novel zebrafish zinc-finger gene, terra, which contains a DNA binding domain similar to that of the Drosophila dsx gene. However, unlike dsx, terra is transiently expressed in the presomitic mesoderm and newly formed somites. Expression of terra in presomitic mesoderm is restricted to cells that lack expression of MyoD. In vivo, terra expression is reduced by hedgehog but enhanced by BMP signals. Overexpression of terra induces rapid apoptosis both in vitro and in vivo, suggesting that a tight regulation of terra expression is required during embryogenesis. Terra has both human and mouse homologs and is specifically expressed in mouse somites. Taken together, our findings suggest that terra is a highly conserved protein that plays specific roles in early somitogenesis of vertebrates.

scholarly journals Chimeric CLL-1 Antibody Fusion Proteins Containing Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-2 With Specificity for B-Cell Malignancies Exhibit Enhanced Effector Functions While Retaining Tumor Targeting Properties

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4437-4447 ◽  
Author(s):  
Jason L. Hornick ◽  
Leslie A. Khawli ◽  
Peisheng Hu ◽  
Maureen Lynch ◽  
Peter M. Anderson ◽  
...  
Keyword(s):  
B Cell ◽  
Fusion Proteins ◽  
Tumor Targeting ◽  
B Cell Malignancies ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Although monoclonal antibody (MoAb) therapy of the human malignant lymphomas has shown success in clinical trials, its full potential for the treatment of hematologic malignancies has yet to be realized. To expand the clinical potential of a promising human-mouse chimeric antihuman B-cell MoAb (chCLL-1) constructed using the variable domains cloned from the murine Lym-2 (muLym-2) hybridoma, fusion proteins containing granulocyte-macrophage colony-stimulating factor (GM-CSF) (chCLL-1/GM–CSF) or interleukin (IL)-2 (chCLL-1/IL–2) were generated and evaluated for in vitro cytotoxicity and in vivo tumor targeting. The glutamine synthetase gene amplification system was employed for high level expression of the recombinant fusion proteins. Antigenic specificity was confirmed by a competition radioimmunoassay against ARH-77 human myeloma cells. The activity of chCLL-1/GM–CSF was established by a colony formation assay, and the bioactivity of chCLL-1/IL–2 was confirmed by supporting the growth of an IL-2–dependent T-cell line. Antibody-dependent cellular cytotoxicity against ARH-77 target cells demonstrated that both fusion proteins mediate enhanced tumor cell lysis by human mononuclear cells. Finally, biodistribution and imaging studies in nude mice bearing ARH-77 xenografts indicated that the fusion proteins specifically target the tumors. These in vitro and in vivo data suggest that chCLL-1/GM–CSF and chCLL-1/IL–2 have potential as immunotherapeutic reagents for the treatment of B-cell malignancies.

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