A5039081890- Monoclonal and Polyclonal Antibodies Research
- Mast cells and histamine
- Immune cells in cancer
- Immune Cell Function and Interaction
- Allergic Rhinitis and Sensitization
- Asthma and respiratory diseases
- Cancer Immunotherapy and Biomarkers
- Food Allergy and Anaphylaxis Research
- T-cell and B-cell Immunology
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Urticaria and Related Conditions
- Chemokine receptors and signaling
- Cancer-related Molecular Pathways
- Advanced Breast Cancer Therapies
- Immunodeficiency and Autoimmune Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Transgenic Plants and Applications
- IL-33, ST2, and ILC Pathways
- Drug-Induced Adverse Reactions
- Protein purification and stability
- Ovarian cancer diagnosis and treatment
- Reproductive System and Pregnancy
King's College London
2016-2025
Guy's Hospital
2016-2025
The London College
2025
Canbex Therapeutics (United Kingdom)
2019
Medical Research Council
2018
Asthma UK
2012-2018
St Thomas' Hospital
2016-2018
University of Cambridge
2015
GlaxoSmithKline (United Kingdom)
2013
The Netherlands Cancer Institute
1991
Background Anti-human epidermal growth factor receptor 2 (HER2) IgG1-based antibody therapies significantly improve cancer prognosis, yet intrinsic or acquired resistance to fragment antigen-binding (Fab)-mediated direct effects commonly occurs. Most resistant tumors retain antigen expression and therefore remain potentially targetable with anti-HER2 that promote immune-mediated responses. Tumor-antigen-specific IgE class antibodies can mediate powerful immune cell-mediated against different...
Abstract Over the last four decades, molecular cloning has evolved tremendously. Efficient products allowing assembly of multiple DNA fragments have become available. However, cost-effective tools for engineering antibodies different specificities, isotypes and species are still needed many research clinical applications in academia. Here, we report a method one-step antibody heavy- light-chain DNAs into single mammalian expression vector, starting from encoding desired variable constant...
Abstract Background Survival rates for ovarian cancer remain poor, and monitoring prediction of therapeutic response may benefit from additional markers. Ovarian cancers frequently overexpress Folate Receptor alpha (FRα) the soluble receptor (sFRα) is measurable in blood. Here we investigated sFRα as a potential biomarker. Methods We evaluated longitudinally, before during neo-adjuvant, adjuvant palliative therapies, tumour FRα expression status by immunohistrochemistry. The impact free on...
Abstract Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal antibody human constant domains recognizing to target melanoma. binds melanomas including...
Abstract Background Tumor-targeting IgE antibodies have elicited potent tumor-restricting effects by recruiting immune effector mechanisms. However, a dedicated platform for the generation, selection and evaluation of novel IgEs based on target antigen recognition functional profiles has not been reported. Methods By establishing an class antibody therapeutic design to allow lead candidates, we generated panel recognising human epidermal growth factor receptor 2 (HER2), overexpressed in...
Abstract Purpose: Highly aggressive triple-negative breast cancers (TNBCs) lack validated therapeutic targets and have high risk of metastatic disease. Folate receptor alpha (FRα) is a central mediator cell growth regulation that could serve as an important target for cancer therapy. Experimental Design: We evaluated FRα expression in by genomic (n = 3,414) IHC 323) analyses its association with clinical parameters outcomes. measured the functional contributions TNBC biology RNA interference...
IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibody-dependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen-specific IgEs were reported to restrict cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms undefined
Abstract All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers potential enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with primary objective exploring safety and tolerability MOv18 chimeric first-in-class IgE antibody, in patients tumours expressing relevant antigen, folate receptor-alpha. The incorporated skin prick basophil activation tests (BAT) to select at...
Some 10 years ago it emerged that at sufficiently high concentrations certain monoclonal mouse IgEs exert previously unsuspected effects on mast cells. Thus they can both promote survival and induce activation of cells without the requirement for antigens. This was a wake up call appears to have been missed (or dismissed) by majority immunologists. The structural attributes responsible potency so-called "highly cytokinergic" or HC not yet determined, but events ensue when such bind...
IgG4 purified from patients undergoing specific allergen immunotherapy inhibits the activities of serum IgE in vitro assays and is thought to reduce symptoms disease. However, it not known whether this related an intrinsic property subclass or only specificity. We tested hypothesis that specificity critical determinant for activity using a panel antibodies with identical but different subclasses. The were all able inhibit same extent. demonstrate dominant factor determining ability antibody...
B cells participate in immune surveillance human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B healthy volunteers melanoma patients (n = 73) CD22+ normal skin samples 189). Normal malignant featured mature IgG CD22 mRNA, alongside mRNA for transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses...
Basophils are involved in manifestations of hypersensitivity, however, the current understanding their propensity for activation and prognostic value cancer patients remains unclear. As healthy atopic individuals, basophil populations were identified blood from ovarian (n = 53) with diverse tumor histologies treatment histories. Ex vivo was measured by CD63 expression using test (BAT). Irrespective prior treatment, basophils could be activated stimulation IgE- (anti-FcεRI anti-IgE) non-IgE...