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Your search keyword '"Clark, Jan"' showing total 12 results
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12 results on '"Clark, Jan"'

1. Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study

Author

Welker, James, primary, Pulido, Juan D, additional, Catanzaro, Andrew T, additional, Malvestutto, Carlos D, additional, Li, Zihai, additional, Cohen, Jonathan B, additional, Whitman, Eric D, additional, Byrne, Dana, additional, Giddings, Olivia K, additional, Lake, Jordan E, additional, Chua, Joel V, additional, Li, Ella, additional, Chen, Jian, additional, Zhou, Xiang, additional, He, Kun, additional, Gates, Davis, additional, Kaur, Amarjot, additional, Chen, Jamie, additional, Chou, Hung-Yen, additional, Devenport, Martin, additional, Touomou, Raymond, additional, Kottilil, Shyamasundaran, additional, Liu, Yang, additional, Zheng, Pan, additional, Thakor, Jai, additional, Khan, Imaan, additional, Do, Nicole, additional, Faragalla, Josephine, additional, Hook, Andrea, additional, Kern, Sarah, additional, Ramos, Janira V., additional, Ward, Jason, additional, Higson, John, additional, Dam, Meena, additional, Serkin, Dawn, additional, Karloopia, Pooja, additional, Moore, Wendy, additional, Scofield, Mark, additional, Childers, David Jeffery, additional, Cantrell, Jeffrey S., additional, Corgan, Millie, additional, Liu, Jing, additional, Redvers-Higgins, Denise, additional, Han, Hua, additional, Hou, Jiyun, additional, Pan, Yudi, additional, Tucker, Karyn, additional, Zhang, Xiaoyan, additional, Chua, Joel V., additional, Husson, Jennifer, additional, Narayanan, Shivakumar, additional, Bran, Jaqueline, additional, Lam, Ka Wing Joyce, additional, Jeffrey, Alicia, additional, Giddings, Olivia K., additional, Pexa, Jennie, additional, Becerra, Mario, additional, Welker, James, additional, Gray, Kathleen W., additional, Richmond, Nicole, additional, Nzelibe, Chukwuemeka, additional, Malvestutto, Carlos D., additional, Koletar, Susan, additional, Sobhanie, Mahdee, additional, Clark, Jan, additional, Reynolds, Kelsi, additional, Chakravarthy, Karthik, additional, Weller, Kevin, additional, Yusuf, Mohamed, additional, Severing, Jennifer, additional, Barley, Kelley, additional, Pulido, Juan D., additional, Fulton, Jennifer C., additional, Gil, William, additional, Jeanine, M.D., additional, R.N., Richmond, additional, Jones, Sandy, additional, Clemmer, Kristina, additional, Pedroza, Lisa, additional, Davidson, Emily Nicole, additional, Logan, Amanda, additional, Grant, Katie, additional, Whitman, Eric D., additional, Kessler, Jason, additional, Roland, Robert, additional, Stefiniw, Rosemary, additional, Maurer, Molly, additional, Geene, Salome, additional, Buck, Christopher F., additional, Connolly, Debra, additional, Light, Patrice, additional, Baviskar, Sunanda, additional, Low, Yee Won, additional, Michalski, Kyra, additional, Giordano, Pamela, additional, Chao, Jennifer, additional, Williams, Michelle, additional, Makkapati, Amulya, additional, Catanzaro, Andrew T., additional, Cohen, Jonathan B., additional, Musbah, Mehad, additional, Jaladanki, Pramila, additional, Yuan, Ying, additional, Rele, Shilpa, additional, Stewart, Desirae, additional, Lewis, Starlet, additional, Sankar, Ian, additional, Kasumba, Nabulungi, additional, Biney, Kaylia, additional, Hekmat, Elham, additional, Lake, Jordan E., additional, Akkanti, Bindu, additional, Reimer-McAtee, Melissa J., additional, and Negret Hernandez, Marisel, additional

Published
2022
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2. Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells

Author

Bell, Charles J.M., Sun, Yongliang, Nowak, Urszula M., Clark, Jan, Howlett, Sarah, Pekalski, Marcin L., Yang, Xin, Ast, Oliver, Waldhauer, Inja, Freimoser-Grundschober, Anne, Moessner, Ekkehard, Umana, Pablo, Klein, Christian, Hosse, Ralf J., Wicker, Linda S., and Peterson, Laurence B.

Subjects
Cytokine therapy, Immunology, Immunology and Allergy, hemic and immune systems, chemical and pharmacologic phenomena, Autoimmunity, Regulatory T cells, Graft versus host disease, IL-2 fusion proteins
Abstract

Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4.

Published
2015
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3. Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells

Author

Bell, Charles JM, Sun, Yongliang, Nowak, Urszula M, Clark, Jan, Howlett, Sarah, Pekalski, Marcin L, Yang, Xin, Ast, Oliver, Waldhauer, Inja, Freimoser-Grundschober, Anne, Moessner, Ekkehard, Umana, Pablo, Klein, Christian, Hosse, Ralf J, Wicker, Linda S, Peterson, Laurence B, and Apollo - University of Cambridge Repository

Subjects
Male, Recombinant Fusion Proteins, Autoimmunity, Graft versus host disease, T-Lymphocytes, Regulatory, Mice, T-Lymphocyte Subsets, Eosinophilia, STAT5 Transcription Factor, Animals, Humans, CTLA-4 Antigen, Lymphocyte Count, Phosphorylation, Cytokine therapy, Mice, Knockout, Dose-Response Relationship, Drug, Interleukin-2 Receptor alpha Subunit, Forkhead Transcription Factors, Regulatory T cells, IL-2 fusion proteins, Recombinant Proteins, Macaca fascicularis, Phenotype, Interleukin-2, Female, Biomarkers, Protein Binding, Signal Transduction
Abstract

Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4.

Published
2015

10. Type 1 diabetes genes and pathways shared by humans and NOD mice

Author

Wicker, Linda S., primary, Clark, Jan, additional, Fraser, Heather I., additional, Garner, Valerie E.S., additional, Gonzalez-Munoz, Andrea, additional, Healy, Barry, additional, Howlett, Sarah, additional, Hunter, Kara, additional, Rainbow, Dan, additional, Rosa, Raymond L., additional, Smink, Luc J., additional, Todd, John A., additional, and Peterson, Laurence B., additional

Published
2005
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