ABSTRACTIntroductionMilitary personnel are exposed to a broad range of potentially toxic compounds that can affect their health. These hazards are unpredictable because military service occurs in a wide array of uncontrolled environments. Therefore, a novel sorbent was developed that allows the fabrication of lightweight personal samplers that are both capable of sorbing an extremely wide range of organic chemical types and able to stabilize reactive compounds.Materials and MethodsOSU-6, a nanoporous silica, was provided by XploSafe LLC. The sorption capacity for several volatile organic compounds, the temperatures required for thermal desorption of adsorbed compounds, and the sampling rates for targeted analytes were determined.ResultsThe uptake capacity was found to be on average 1.5 g/g of sorbent. Analytes were not only held tightly but also could be desorbed upon heating the sorbate to temperatures below 150°C. Sampling rates for volatile organic compound by an OSU-6 sampler badge were on average, 5.7 times higher than those for a commercially available activated carbon badge. Theoretical calculations showed that sorption of volatile organic compounds on the surface of the tightly curved pore walls in OSU-6 is because of exceptionally strong cumulative addition of Van der Waals forces. Analytes could readily be analyzed by either solvent extraction or thermal desorption gas chromatography/mass spectrometry techniques. Excellent sampling rates, high concentrations of analytes in the OSU-6 sorbent matrix, and high desorption efficiencies (recoveries) were obtained using the thermal desorption method.ConclusionsThe performance of the OSU-6 sorbent makes it highly capable of meeting the need for personal samplers that enable Individual Longitudinal Exposure Records development. It can adsorb an extremely wide array of different volatile organic compounds, it can stabilize reactive compounds, it has high sampling rates coupled with high capacity that provide both sensitivity and resistance to saturation, and it is unique in being very amenable to thermal desorption in combination with having strong sorbate binding and high capacity and surface area.

Communications Biology

Discovery of an agonistic Siglec-6 antibody that inhibits and reduces human mast cells

Article

Author: Luu, Thuy ; Chang, Katherine ; Wong, Alan ; Benet, Zachary ; Leung, John ; Korver, Wouter ; Youngblood, Bradford A ; Luehrsen, Kenneth ; Brehm, Michael A ; De Freitas, Naomi ; Brock, Emily C ; Schanin, Julia ; Xu, Alan

AbstractMast cells (MC) are key drivers of allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-6 is an immunoregulatory receptor found on MCs. While it is recognized that engaging Siglecs with antibodies mediates inhibition across immune cells, the mechanisms that govern this agonism are not understood. Here we generated Siglec-6 mAb clones (AK01 to AK18) to better understand Siglec-6-mediated agonism. Siglec-6 mAbs displayed epitope-dependent receptor internalization and inhibitory activity. We identified a Siglec-6 mAb (AK04) that required Fc-mediated interaction for receptor internalization and induced inhibition and antibody-dependent cellular phagocytosis against MCs. AK04-mediated MC inhibition required Siglec-6 immunoreceptor tyrosine-based inhibitory motif (ITIM) and ITIM-like domains and was associated with receptor cluster formation containing inhibitory phosphatases. Treatment of humanized mice with AK04 inhibited systemic anaphylaxis with a single dose and reduced MCs with chronic dosing. Our findings suggest Siglec-6 activity is epitope dependent and highlight an agonistic Siglec-6 mAb as a potential therapeutic approach in allergic disease.

Nature Communications

Siglec-6 as a therapeutic target for cell migration and adhesion in chronic lymphocytic leukemia

Article

Author: Cyr, Matthew G ; Mo, Xiaokui ; Tafesse, Rakeb ; Purcell, Matthew ; Mao, Charlene ; Long, Meixiao ; Rader, Christoph ; Muthusamy, Natarajan ; Nunes, Jessica ; Zhang, Liwen

AbstractSiglec-6 is a lectin receptor with restricted expression in the placenta, mast cells and memory B-cells. Although Siglec-6 is expressed in patients with chronic lymphocytic leukemia (CLL), its pathophysiological role has not been elucidated. We describe here a role for Siglec-6 in migration and adhesion of CLL B cells to CLL- bone marrow stromal cells (BMSCs) in vitro and compromised migration to bone marrow and spleen in vivo. Mass spectrometry analysis revealed interaction of Siglec-6 with DOCK8, a guanine nucleotide exchange factor. Stimulation of MEC1-002 CLL cells with a Siglec-6 ligand, sTn, results in Cdc42 activation, WASP protein recruitment and F-actin polymerization, which are all associated with cell migration. Therapeutically, a Siglec-6/CD3-bispecific T-cell-recruiting antibody (T-biAb) improves overall survival in an immunocompetent mouse model and eliminates CLL cells in a patient derived xenograft model. Our findings thus reveal a migratory role for Siglec-6 in CLL, which can be therapeutically targeted using a Siglec-6 specific T-biAb.

100 Deals associated with Siglec-6/CD3 targeted bispecific antibody(OSU)

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphoid Leukemia	Preclinical	US	The Ohio State University	17 Apr 2023

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