Sha Klabunde

Engineering a protease-stable, oral single-domain antibody to inhibit IL-23 signaling

Naruhisa Ota, C. Davies, Jing‐Qiong Kang, Donghong Yan et autres

Interleukin (IL)-23 is a validated therapeutic target in inflammatory bowel disease. While antibodies targeting IL23 demonstrate clinical efficacy, they face challenges such as high costs, safety risks, and the necessity of parenteral administration. Here, we present a workflow to simultaneously enhance the …

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A phase I, randomized, ascending‐dose study to assess safety, pharmacokinetics, and activity of GDC‐8264, a RIP1 inhibitor, in healthy volunteers

Nicholas S. Jones, Smita Kshirsagar, Vishnu Mohanan, Vidya Ramakrishnan et autres

Receptor-interacting protein 1 (RIP1) is a key regulator of multiple signaling pathways that mediate inflammatory responses and cell death. RIP1 kinase activity mediates apoptosis and necroptosis induced by tumor necrosis factor (TNF)-α, Toll-like receptors, and ischemic tissue damage. RIP1 has been implicated …

Regulation and Role of αE Integrin and Gut Homing Integrins in Migration and Retention of Intestinal Lymphocytes during Inflammatory Bowel Disease

Mary Keir, Franklin Fuh, Ryan Ichikawa, Meghan Acres et autres

Abstract Targeting interactions between α4β7 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses αEβ7 integrin, …

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The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells

Cesar A. Corzo, Eugene Varfolomeev, Audi Setiadi, Ross Francis et autres

The dysregulation of multiple signaling pathways, including those through endosomal Toll-like receptors (TLRs), Fc gamma receptors (FcγR), and antigen receptors in B cells (BCR), promote an autoinflammatory loop in systemic lupus erythematosus (SLE). Here, we used selective small-molecule inhibitors to assess the …

Cellular Mechanisms of Etrolizumab Treatment in Inflammatory Bowel Disease

Charlotte Lichnog, Sha Klabunde, Emily Becker, Franklin Fuh et autres

Background: Anti-integrin therapy is a new frontline strategy in the treatment of inflammatory bowel diseases (IBD). The anti-β7 integrin antibody etrolizumab is currently being investigated for safety and efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in several phase III trials. …

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HCD122, on human chronic lymphocytic leukemia cells The antileukemia activity of a human anti-CD40 antagonist antibody,

Bahija Jallal, Natasha Aziz, Wen‐Kai Weng, William G. Wierda et autres

doi:10.1182/blood-2007-04-084756Prepublished online May 22, 2008;2008 112: 711-720€€€€Bahija Jallal, Natasha Aziz, Wen-Kai Weng, William Wierda, Susan O'Brien and Anas YounesHolash, Cheryl Goldbeck, Xiaomei Xu, Edward E. Kadel III, Sang Hoon Lee, Sharon Lea Aukerman, Mohammad Luqman, Sha Klabunde, Karen Lin, Georgios V. Georgakis, …

Sa2025 Etrolizumab-Mediated Ex Vivo Modulation of Beta7 Cell Surface Receptors in Nonhuman Primate and Human Peripheral Blood Supports the Proposed Mechanism of Action

Marna Williams, Sha Klabunde, Franklin Fuh, Clarissa F. Johnson et autres

The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells

Mohammad Luqman, Sha Klabunde, Karen Lin, Georgios Georgakis et autres

B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well as the receptor CD40. Activation of CD40 by its ligand (CD40L) induces proliferation and rescues the cells from spontaneous and chemotherapy-induced apoptosis. …

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HCD122, an Antagonist Human Anti-CD40 Monoclonal Antibody, Enhances Efficacy of CHOP in Tumor Xenograft Model of Human Diffuse Large B-Cell Lymphoma.

Mohammad Luqman, Ssucheng J. Hsu, Matthew Ericson, Sha Klabunde et autres

Abstract HCD122 (formerly known as CHIR-12.12), is a fully human anti-CD40 monoclonal antibody (mAb) currently in Phase I clinical trials for treatment of chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). An IgG1 antibody selected for its potency as an antagonist of …

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