6 results on '"Josephs, Debra H."'
Search Results
2. AllergoOncology: Danger signals in allergology and oncology: A European Academy of Allergy and Clinical Immunology (EAACI) Position Paper.
- Author
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Bergmann, Christoph, Poli, Aurélie, Agache, Ioana, Bianchini, Rodolfo, Bax, Heather J., Castells, Mariana, Crescioli, Silvia, Dombrowicz, David, Ferastraoaru, Denisa, Fiebiger, Edda, Gould, Hannah J., Hartmann, Karin, Izquierdo, Elena, Jordakieva, Galateja, Josephs, Debra H., Jutel, Marek, Levi‐Schaffer, Francesca, de las Vecillas, Leticia, Lotze, Michael T., and Osborn, Gabriel
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CLINICAL immunology ,ALLERGIES ,AUTOIMMUNE diseases ,IMMUNE response ,HAZARDS ,DISEASE risk factors - Abstract
The immune system interacts with many nominal 'danger' signals, endogenous danger‐associated (DAMP), exogenous pathogen (PAMP) and allergen (AAMP)‐associated molecular patterns. The immune context under which these are received can promote or prevent immune activating or inflammatory mechanisms and may orchestrate diverse immune responses in allergy and cancer. Each can act either by favouring a respective pathology or by supporting the immune response to confer protective effects, depending on acuity or chronicity. In this Position Paper under the collective term danger signals or DAMPs, PAMPs and AAMPs, we consider their diverse roles in allergy and cancer and the connection between these in AllergoOncology. We focus on their interactions with different immune cells of the innate and adaptive immune system and how these promote immune responses with juxtaposing clinical outcomes in allergy and cancer. While danger signals present potential targets to overcome inflammatory responses in allergy, these may be reconsidered in relation to a history of allergy, chronic inflammation and autoimmunity linked to the risk of developing cancer, and with regard to clinical responses to anti‐cancer immune and targeted therapies. Cross‐disciplinary insights in AllergoOncology derived from dissecting clinical phenotypes of common danger signal pathways may improve allergy and cancer clinical outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Basophil activation test in cancer patient blood evaluating potential hypersensitivity to an anti‐tumor IgE therapeutic candidate.
- Author
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Bax, Heather J., Khiabany, Atousa, Stavraka, Chara, Pellizzari, Giulia, Chan Wah Hak, Charleen, Robinson, Alexandra, Ilieva, Kristina M., Woodman, Natalie, Naceur‐Lombardelli, Cristina, Gillett, Cheryl, Pinder, Sarah, Gould, Hannah J., Corrigan, Christopher J., Till, Stephen J., Katugampola, Sidath, Barton, Claire, Winship, Anna, Ghosh, Sharmistha, Montes, Ana, and Josephs, Debra H.
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BASOPHILS ,HEMATOLOGIC malignancies ,CANCER patients ,ALLERGIES ,DRUG allergy ,MEDICAL sciences - Abstract
Basophil activation test in cancer patient blood evaluating potential hypersensitivity to an anti-tumor IgE therapeutic candidate Keywords: basophils; BAT; IgE; MOv18; ovarian cancer EN basophils BAT IgE MOv18 ovarian cancer 1 5 5 07/29/20 20200801 NES 200801 To the Editor, Monoclonal anti-tumor IgG antibodies are used widely to treat malignancies. These include superior affinity of IgE for cognate Fc receptors and the presence in tumors of effector cell populations (eg, macrophages and mast cells) known to exert anti-tumor activities when activated by IgE. [Extracted from the article]
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- 2020
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4. AllergoOncology: Expression platform development and functional profiling of an anti‐HER2 IgE antibody.
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Ilieva, Kristina M., Fazekas‐Singer, Judit, Bax, Heather J., Crescioli, Silvia, Montero‐Morales, Laura, Mele, Silvia, Sow, Heng Sheng, Stavraka, Chara, Josephs, Debra H., Spicer, James F., Steinkellner, Herta, Jensen‐Jarolim, Erika, Tutt, Andrew N. J., and Karagiannis, Sophia N.
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IMMUNOGLOBULINS ,MEDICAL sciences ,IMMUNOGLOBULIN E ,ALLERGIC conjunctivitis ,EXPERIMENTAL medicine ,BLOOD cells ,MEDICAL research - Abstract
Building upon ours and others' previous methodologies, we report the efficient transient expression and functional evaluation of IgE, exemplified using the variable region sequences of trastuzumab and human IgE constant regions (anti-HER2 IgE). Like trastuzumab, anti-HER2 IgE recognized HER2/ I neu i -overexpressing (BT-474, ZR75-30) breast cancer cells and moderately expressing MCF-10 normal breast cells, and its HER2 antigen recognition kinetic profile on tumour cells was comparable to trastuzumab (Figure A). Importantly, the lack of anti-HER2 IgE blood basophil activation points to diminishing potential safety concerns associated with using IgE class antibodies in cancer immunotherapy. Harnessing engineered antibodies of the IgE class to combat malignancy: initial assessment of FcvarepsilonRI-mediated basophil activation by a tumour-specific IgE antibody to evaluate the risk of type I hypersensitivity. [Extracted from the article]
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- 2019
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5. AllergoOncology: Microbiota in allergy and cancer—A European Academy for Allergy and Clinical Immunology position paper.
- Author
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Untersmayr, Eva, Bax, Heather J., Bergmann, Christoph, Bianchini, Rodolfo, Cozen, Wendy, Gould, Hannah J., Hartmann, Karin, Josephs, Debra H., Levi‐Schaffer, Francesca, Penichet, Manuel L., O'Mahony, Liam, Poli, Aurelie, Redegeld, Frank A., Roth‐Walter, Franziska, Turner, Michelle C., Vangelista, Luca, Karagiannis, Sophia N., and Jensen‐Jarolim, Erika
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CLINICAL immunology ,ALLERGIES ,CROSSTALK ,IMMUNOLOGICAL tolerance ,CANCER - Abstract
The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome. [ABSTRACT FROM AUTHOR]
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- 2019
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6. Development of downstream processing to minimize beta-glucan impurities in GMP-manufactured therapeutic antibodies.
- Author
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Vigor, Kim, Emerson, John, Scott, Robert, Cheek, Julia, Barton, Claire, Bax, Heather J., Josephs, Debra H., Karagiannis, Sophia N., Spicer, James F., and Lentfer, Heike
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BETA-glucans ,BIOLOGICAL products ,IMMUNOGLOBULINS ,CURRENT good manufacturing practices ,POLLUTANTS ,POLYSACCHARIDES ,MONOMERS - Abstract
The presence of impurities or contaminants in biological products such as monoclonal antibodies (mAb) could affect efficacy or cause adverse reactions in patients. ICH guidelines (Q6A and Q6B) are in place to regulate the level of impurities within clinical drug products. An impurity less often reported and, therefore, lacking regulatory guideline is beta-glucan. Beta-glucans are polysaccharides of d-glucose monomers linked by (1-3) beta-glycosidic bonds, and are produced by prokaryotic and eukaryotic organisms, including plants. They may enter manufacturing processes via raw materials such as cellulose-based membrane filters or sucrose. Here we report the detection of beta-glucan contamination of a monoclonal IgE antibody (MOv18), manufactured in our facility for a first-in-human, first-in-class clinical trial in patients with cancer. Since beta-glucans have potential immunostimulatory properties and can cause symptomatic infusion reactions, it was of paramount importance to identify the source of beta-glucans in our product and to reduce the levels to clinically insignificant concentrations. We identified beta-glucans in sucrose within the formulation buffer and within the housing storage buffer of the virus removal filter. We also detected low level beta-glucan contamination in two of four commercially available antibodies used in oncology. Both formulation buffers contained sucrose. We managed to reduce levels of beta-glucan in our product 10-fold, by screening all sucrose raw material, filtering the sucrose by Posidyne® membrane filtration, and by incorporating extra wash steps when preparing the virus removal filter. The beta-glucan levels now lie within a range that is unlikely to cause clinically significant immunological effects. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1494-1502, 2016 [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
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