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Elizabeth P. St. John Birgitte B. Simen Gregory S. Turenchalk Michael S. Braverman Isabella Abbate Jeroen Aerssens Olivier Bouchez Christian Gabriel Jacques Izopet Karolin Meixenberger Francesca Di Giallonardo Ralph Schlapbach Roger Paredes James Sakwa Gudrun G. Schmitz-Agheguian Alexander Thielen Martin Victor Karin J. Metzner Martin P. D?umer HIV- Alpha Study Group 《PloS one》2016,11(1)
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Michela Silacci Wibke Lembke Richard Woods Isabella Attinger-Toller Nadja Baenziger-Tobler Sarah Batey 《MABS-AUSTIN》2016,8(1):141-149
Biologic treatment options such as tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of inflammatory diseases, including rheumatoid arthritis. Recent data suggest, however, that full and long-lasting responses to TNF inhibitors are limited because of the activation of the pro-inflammatory TH17/interleukin (IL)-17 pathway in patients. Therefore, dual TNF/IL-17A inhibition is an attractive avenue to achieve superior efficacy levels in such diseases. Based on the marketed anti-TNF antibody adalimumab, we generated the bispecific TNF/IL-17A-binding FynomAb COVA322. FynomAbs are fusion proteins of an antibody and a Fyn SH3-derived binding protein. COVA322 was characterized in detail and showed a remarkable ability to inhibit TNF and IL-17A in vitro and in vivo. Through its unique mode-of-action of inhibiting simultaneously TNF and the IL-17A homodimer, COVA322 represents a promising drug candidate for the treatment of inflammatory diseases. COVA322 is currently being tested in a Phase 1b/2a study in psoriasis (ClinicalTrials.gov Identifier: NCT02243787). 相似文献
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Sara Heidl Isabella Ellinger Verena Niederberger Eva E. Waltl Renate Fuchs 《Protoplasma》2016,253(6):1557-1564
The airway epithelium is a central player in the defense against pathogens including efficient mucociliary clearance and secretion of immunoglobulins, mainly polymeric IgA, but also IgG. Pulmonary administration of therapeutic antibodies on one hand, and intranasal immunization on the other, are powerful tools to treat airway infections. In either case, the airway epithelium is the primary site of antibody transfer. In various epithelia, bi-polar transcytosis of IgG and IgG immune complexes is mediated by the human neonatal Fc receptor, FcRn, but FcRn expression in the nasal epithelium had not been demonstrated, so far. We prepared affinity-purified antibodies against FcRn α-chain and confirmed their specificity by Western blotting and immunofluorescence microscopy. These antibodies were used to study the localization of FcRn α-chain in fixed nasal tissue. We here demonstrate for the first time that ciliated epithelial cells, basal cells, gland cells, and endothelial cells in the underlying connective tissue express the receptor. A predominant basolateral steady state distribution of the receptor was observed in ciliated epithelial as well as in gland cells. Co-localization of FcRn α-chain with IgG or with early sorting endosomes (EEA1-positive) but not with late endosomes/lysosomes (LAMP-2-positive) in ciliated cells was observed. This is indicative for the presence of the receptor in the recycling/transcytotic pathway but not in compartments involved in lysosomal degradation supporting the role of FcRn in IgG transcytosis in the nasal epithelium. 相似文献
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Zeynep Eroglu Sheri L. Holmen Qing Chen Nikhil I. Khushalani Ravi Amaravadi Reena Thomas Kamran A. Ahmed Hussein Tawbi Sunandana Chandra Joseph Markowitz Inna Smalley James K. C. Liu Yian Ann Chen Yana G. Najjar Florian A. Karreth Daniel Abate‐Daga Isabella C. Glitza Jeffrey A. Sosman Vernon K. Sondak Marcus Bosenberg Meenhard Herlyn Michael B. Atkins Harriet Kluger Kim Margolin Peter A. Forsyth Michael A. Davies Keiran S. M. Smalley 《Pigment cell & melanoma research》2019,32(3):458-469
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area. 相似文献
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