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Article: Notch and T Cell Function - A Complex Tale.

Vijayaraghavan, Jyothi / Osborne, Barbara A

Advances in experimental medicine and biology

2018 Volume 1066, Page(s) 339–354

Abstract: Notch drives critical decisions in a multitude of developmental decisions in many invertebrate and vertebrate organisms including flies, worms, fish, mice and humans. Therefore, it is not surprising that Notch family members also play a key role in cell ... ...

Abstract	Notch drives critical decisions in a multitude of developmental decisions in many invertebrate and vertebrate organisms including flies, worms, fish, mice and humans. Therefore, it is not surprising that Notch family members also play a key role in cell fate choices in the vertebrate immune system. This review highlights the critical function of Notch in the development of mature T lymphocytes from hematopoietic precursors and describes the role of Notch in mature T cell activation, proliferation and differentiation.
MeSH term(s)	Animals ; Cell Differentiation/immunology ; Cell Proliferation/physiology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/immunology ; Humans ; Lymphocyte Activation ; Receptors, Notch/immunology ; Signal Transduction/immunology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology
Chemical Substances	Receptors, Notch
Language	English
Publishing date	2018-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-89512-3_17
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Notch, a T-ALL order.

Osborne, Barbara A

Blood

2011 Volume 117, Issue 10, Page(s) 2749–2750

Language	English
Publishing date	2011-03-10
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2011-01-330225
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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: Protein-Antibody Conjugates (PACs): A Plug-and-Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins.

Liu, Bin / Singh, Khushboo / Gong, Shuai / Canakci, Mine / Osborne, Barbara A / Thayumanavan, S

Angewandte Chemie (International ed. in English)

2021 Volume 60, Issue 23, Page(s) 12813–12818

Abstract: We report here on protein-antibody conjugates (PACs) that are used for antibody-directed delivery of protein therapeutics to specific cells. PACs have the potential to judiciously combine the merits of two prolific therapeutic approaches-biologics and ... ...

Abstract	We report here on protein-antibody conjugates (PACs) that are used for antibody-directed delivery of protein therapeutics to specific cells. PACs have the potential to judiciously combine the merits of two prolific therapeutic approaches-biologics and antibody-drug conjugates. We utilize spherical polymer brushes to construct PACs using the combination of two simple and efficient functionally orthogonal click chemistries. In addition to the synthesis and characterization of these nanoparticles, we demonstrate that PACs are indeed capable of specifically targeting cells based on the presence of target antigen on the cell surface to deliver proteins. The potentially broad adaptability of PACs opens up new opportunities for targeted biologics in therapeutics and sensing.
MeSH term(s)	Antibodies/chemistry ; Cell Line, Tumor ; Fullerenes/chemistry ; Humans ; Nanoparticles/chemistry ; Particle Size ; Receptor, ErbB-2/chemistry
Chemical Substances	Antibodies ; Fullerenes ; pristine (C60) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2021-05-05
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202103106
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Article ; Online: Evaluation of Cellular Targeting by Fab' vs Full-Length Antibodies in Antibody-Nanoparticle Conjugates (ANCs) Using CD4 T-cells.

Singh, Khushboo / Canakci, Mine / Kanjilal, Pintu / Williams, Natalie / Shanthalingam, Sudarvili / Osborne, Barbara A / Thayumanavan, S

Bioconjugate chemistry

2022 Volume 33, Issue 3, Page(s) 486–495

Abstract: Targeted delivery of chemotherapeutic drugs can improve their therapeutic efficiency by localizing their toxic effects at the diseased site. This is often achieved either by direct conjugation of drugs to antibodies targeting overexpressed receptors on ... ...

Abstract	Targeted delivery of chemotherapeutic drugs can improve their therapeutic efficiency by localizing their toxic effects at the diseased site. This is often achieved either by direct conjugation of drugs to antibodies targeting overexpressed receptors on cancer cells (antibody-drug conjugates/ADCs) or by conjugating antibodies to nanoparticles bearing drugs (antibody-nanoparticle conjugates/ANCs). Here, we report a platform for utilizing hinge cysteines on antigen-binding fragment (Fab') of an anti-CD4 antibody for site-specific conjugation to nanoparticles giving rise to anti-CD4 Fab'-nanoparticle conjugates (Fab'-NCs). We demonstrate a convenient route for obtaining functional anti-CD4 Fab' from full-length antibody and examine the targeted delivery efficiencies of anti-CD4 Fab'-NCs vs ANCs for selective delivery to CD4
MeSH term(s)	Antibodies, Monoclonal ; CD4-Positive T-Lymphocytes ; Immunoconjugates ; Immunoglobulin Fab Fragments ; Nanoparticles
Chemical Substances	Antibodies, Monoclonal ; Immunoconjugates ; Immunoglobulin Fab Fragments
Language	English
Publishing date	2022-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.2c00024
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Article ; Online: B-CLL kicks it up a Notch.

Osborne, Barbara A

Blood

2009 Volume 113, Issue 4, Page(s) 765–766

Language	English
Publishing date	2009-01-21
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2008-10-182998
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Article: Non-canonical notch signaling in cancer and immunity.

Ayaz, Furkan / Osborne, Barbara A

Frontiers in oncology

2014 Volume 4, Page(s) 345

Abstract: Canonical Notch signaling is initiated by γ-secretase-mediated cleavage of the Notch receptor, leading to the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-Jκ, resulting in the activation of ... ...

Abstract	Canonical Notch signaling is initiated by γ-secretase-mediated cleavage of the Notch receptor, leading to the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-Jκ, resulting in the activation of downstream target genes. While canonical Notch signaling is well known to play an active role in several steps during development as well in multiple cell fate decisions, recent evidence from both invertebrate and vertebrate systems indicates that non-canonical, RBP-Jκ-independent signaling is important in several cellular processes including oncogenesis and activation of T lymphocytes. These observations raise the possibility that, through an understanding of non-canonical Notch signaling, novel strategies for inhibiting Notch signaling may prove useful in the design of therapies targeted to block aberrant Notch activity. In this mini-review, we will examine the current data demonstrating a non-canonical role for Notch signaling in both cancer and the immune system and suggest a better understanding of non-canonical signaling may reveal novel strategies to block Notch signaling in disease.
Language	English
Publishing date	2014-12-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2014.00345
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Article ; Online: Targeting Notch in oncology: the path forward.

Majumder, Samarpan / Crabtree, Judy S / Golde, Todd E / Minter, Lisa M / Osborne, Barbara A / Miele, Lucio

Nature reviews. Drug discovery

2020 Volume 20, Issue 2, Page(s) 125–144

Abstract: Notch signalling is involved in many aspects of cancer biology, including angiogenesis, tumour immunity and the maintenance of cancer stem-like cells. In addition, Notch can function as an oncogene and a tumour suppressor in different cancers and in ... ...

Abstract	Notch signalling is involved in many aspects of cancer biology, including angiogenesis, tumour immunity and the maintenance of cancer stem-like cells. In addition, Notch can function as an oncogene and a tumour suppressor in different cancers and in different cell populations within the same tumour. Despite promising preclinical results and early-phase clinical trials, the goal of developing safe, effective, tumour-selective Notch-targeting agents for clinical use remains elusive. However, our continually improving understanding of Notch signalling in specific cancers, individual cancer cases and different cell populations, as well as crosstalk between pathways, is aiding the discovery and development of novel investigational Notch-targeted therapeutics.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/metabolism ; Drug Delivery Systems/methods ; Drug Delivery Systems/trends ; Humans ; Immunotherapy/methods ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/therapy ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/metabolism ; Receptors, Notch/immunology ; Receptors, Notch/metabolism ; Signal Transduction/drug effects ; Signal Transduction/physiology
Chemical Substances	Antineoplastic Agents ; Receptors, Notch
Language	English
Publishing date	2020-12-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-020-00091-3
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Zs.A 5564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Exopolysaccharide-Treated Dendritic Cells Effectively Ameliorate Acute Graft-versus-Host Disease.

Kalinina, Olga / Minter, Lisa M / Sperling, Anne I / Hollinger, Maile K / Le, Phong / Osborne, Barbara A / Zhang, Shubin / Stiff, Patrick / Knight, Katherine L

Transplantation and cellular therapy

2023 Volume 30, Issue 1, Page(s) 79.e1–79.e10

Abstract: Graft-versus-host disease (GVHD) is a primary and often lethal complication of allogenic hematopoietic stem cell transplantation (HSCT). Prophylactic regimens for GVHD are given as standard pretransplantation therapy; however, up to 50% of these patients ...

Abstract	Graft-versus-host disease (GVHD) is a primary and often lethal complication of allogenic hematopoietic stem cell transplantation (HSCT). Prophylactic regimens for GVHD are given as standard pretransplantation therapy; however, up to 50% of these patients develop acute GVHD (aGVHD) and require additional immunosuppressive intervention. Using a mouse GVHD model, we previously showed that injecting mice with exopolysaccharide (EPS) from Bacillus subtilis prior to GVHD induction significantly increased 80-day survival after transplantation of complete allogeneic major histocompatibility complex-mismatched cells. To ask whether EPS might also inhibit GVHD in humans, we used humanized NSG-HLA-A2 mice and induced GVHD by i.v. injection of A2
MeSH term(s)	Animals ; Humans ; Transplantation, Homologous/adverse effects ; HLA-A2 Antigen ; Leukocytes, Mononuclear ; Graft vs Host Disease/prevention & control ; Disease Models, Animal ; Dendritic Cells
Chemical Substances	HLA-A2 Antigen
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2023.10.023
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Zs.A 5082: Show issues

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Article ; Online: LKB1 isoform expression modulates T cell plasticity downstream of PKCθ and IL-6.

Mohan, Deeksha / Sherman, Heather L / Mitra, Ankita / Lawlor, Rebecca / Shanthalingam, Sudarvili / Ullom, Jacob / Pobezinskaya, Elena L / Zhang, Guodong / Osborne, Barbara A / Pobezinsky, Leonid A / Tew, Gregory N / Minter, Lisa M

Molecular immunology

2023 Volume 157, Page(s) 129–141

Abstract: Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as ... ...

Abstract	Following activation, CD4 T cells undergo metabolic and transcriptional changes as they respond to external cues and differentiate into T helper (Th) cells. T cells exhibit plasticity between Th phenotypes in highly inflammatory environments, such as colitis, in which high levels of IL-6 promote plasticity between regulatory T (Treg) cells and Th17 cells. Protein Kinase C theta (PKCθ) is a T cell-specific serine/threonine kinase that promotes Th17 differentiation while negatively regulating Treg differentiation. Liver kinase B1 (LKB1), also a serine/threonine kinase and encoded by Stk11, is necessary for Treg survival and function. Stk11 can be alternatively spliced to produce a short variant (Stk11
MeSH term(s)	Protein Kinase C-theta/metabolism ; Interleukin-6/metabolism ; Cell Plasticity ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; CD4-Positive T-Lymphocytes/metabolism ; T-Lymphocytes, Regulatory/metabolism ; Cell Differentiation ; Protein Isoforms/metabolism ; Th17 Cells/metabolism
Chemical Substances	Protein Kinase C-theta (EC 2.7.11.13) ; Interleukin-6 ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Protein Isoforms
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2023.03.020
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Article: Targeting CD4⁺ Cells with Anti-CD4 Conjugated Mertansine-Loaded Nanogels

Canakci, Mine / Singh, Khushboo / Munkhbat, Oyuntuya / Shanthalingam, Sudarvili / Mitra, Ankita / Gordon, Mallory / Osborne, Barbara A / Thayumanavan, S

Biomacromolecules. 2020 May 08, v. 21, no. 6

2020

Abstract: CD4⁺ T lymphocytes play an important role in controlling many malignancies. The modulation of CD4⁺ T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, ... ...

Abstract	CD4⁺ T lymphocytes play an important role in controlling many malignancies. The modulation of CD4⁺ T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, and cancer. Here, we demonstrate that anti-CD4 conjugated polymeric nanogels can deliver a small molecule cargo to primary CD4⁺ T cells and a CD4ʰⁱᵍʰ T cell lymphoma. The antibody conjugation not only increased the uptake efficiency of the nanogel (NG) by CD4⁺ T cells but also decreased the non-specific uptake of the NG by CD4– lymphocytes. For T lymphoma cell lines, the mertansine-loaded conjugate displayed a dose-dependent cell growth inhibition at 17 ng/mL antibody concentration. On the other hand, antibody-drug conjugate (ADC)-type formulation of the anti-CD4 reached similar levels of cell growth inhibition only at the significantly higher concentration of 1.8 μg/mL. NG and antibody conjugates have the advantage of carrying a large payload to a defined target in a more efficient manner as it needs far less antibody to achieve a similar outcome.
Keywords	T-cell lymphoma ; antibodies ; autoimmunity ; cell growth ; cytotoxicity ; disease progression ; dose response ; growth retardation ; immunosuppression ; nanogels ; neoplasm cells ; polymers
Language	English
Dates of publication	2020-0508
Size	p. 2473-2481.
Publishing place	American Chemical Society
Document type	Article
Note	NAL-AP-2-clean
ISSN	1526-4602
DOI	10.1021/acs.biomac.0c00442
Database	NAL-Catalogue (AGRICOLA)

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