A5081500106- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Diabetes and associated disorders
- Glycosylation and Glycoproteins Research
- Atherosclerosis and Cardiovascular Diseases
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Immune cells in cancer
- Advanced Biosensing Techniques and Applications
- Chemokine receptors and signaling
- Immunotoxicology and immune responses
- Complement system in diseases
- Advanced biosensing and bioanalysis techniques
- Lymphoma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Microfluidic and Bio-sensing Technologies
- Psoriasis: Treatment and Pathogenesis
Genmab (Netherlands)
2024-2025
University College London
2014-2023
Genmab (United States)
2023
The Royal Free Hospital
2019-2020
Centre for Immunity, Infection and Evolution
2015
University of Manchester
2014
Total tumor clearance through immunotherapy is associated with a fully coordinated innate and adaptive immune response, but knowledge on the exact contribution of each cell subset limited. We show that therapy-induced intratumoral CD8+ T cells recruited skewed late-stage activated M1-like macrophages, which were critical for effective control in two different murine models cancer immunotherapy. The summon these macrophages into their close vicinity via CCR5 signaling. Exposure non-polarized...
Significance The inhibitory protein cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is recognized as a crucial regulator of autoimmunity, but its precise mechanism action not yet fully understood. CTLA-4 can down-regulate expression the costimulatory ligands CD80 and CD86 on antigen presenting cells, thereby reducing T-cell CD28 engagement. Here we demonstrate that quantitative changes in level engagement have functional consequences for differentiation toward follicular helper T cells...
CTLA-4 transendocytosis is elicited by self-antigens and down-regulates costimulatory ligands on migratory dendritic cells.
Abstract CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles lack sufficient T-cell infiltrate. Here, we show that pre-treatment vaccination, even when composed tumor-unrelated antigens, induces CXCR3-mediated influx immunologically ‘cold’ tumor models male mice. In absence bsAb, infiltrate confined to invasive margin, whereas subsequent bsAb administration...
CD3 bispecific antibody (CD3 bsAb) therapy has become an established treatment modality for some cancer types and exploits endogenous T cells irrespective of their specificity. However, durable clinical responses are hampered by immune escape through loss tumor target antigen expression. Induction long-lasting tumor-specific immunity might therefore improve therapeutic efficacy, but not been studied in detail yet bsAbs. Here, we examined multiple combination strategies aiming to survival...
Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), archetypal follicular helper T cell (Tfh) cytokine, shapes scale and polarization spontaneous chronic autoimmune as well transient immunization-induced GC. We find IL-21 receptor deficiency results smaller GC are profoundly skewed toward a light zone B phenotype plays key role selection cells for entry to dark zone. Light skewing previously mice lacking cycle...
Abstract Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback this approach impaired regulatory homeostasis that requires signaling. Therefore, strategies restrict the effects blockade cells would be advantageous. Here we probe relative roles IL-2 maintaining Treg. We find provision counteracts loss induced by while minimally affecting conventional compartment. These...
The aryl hydrocarbon receptor (AhR) has been shown to be required for optimal Thelper (Th) 17 cell activation. Th17 cells provide immunity against extracellular pathogens and are implicated in autoimmune diseases. Herein, the role of AhR cytokine production by Th17, analogous population T cytotoxic (Tc)17 cells, examined. Lymph node Tc (CD8(+)) Th (CD4(+)) were isolated negative selection from naive AhR(+/-) AhR(-/-) mice polarised Tc1/Th1 or Tc17/Th17 phenotypes with appropriate cytokines....
Summary Efficacy of checkpoint inhibitor therapies in cancer varies greatly, with some patients showing complete responses while others do not respond and experience progressive disease. We aimed to identify correlates response progression following PD-1-directed therapy by immunophenotyping peripheral blood samples from 20 advanced malignant melanoma before after treatment the PD-1 blocking antibody pembrolizumab. Our data reveal that individuals responding blockade were characterised...
Abstract CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles lack sufficient T-cell infiltrate. Here, we show that pre-treatment vaccinations, even when they comprised tumor-unrelated antigens, induced CXCR3-mediated influx immunologically ‘cold’ mouse tumor models. In absence bsAb, infiltrate was mainly confined to invasive margin, however subsequent bsAb...