Iva Zlatareva
A5082427195- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Immune responses and vaccinations
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Immune Response and Inflammation
- COVID-19 and healthcare impacts
- Medical Imaging Techniques and Applications
- Peptidase Inhibition and Analysis
- HER2/EGFR in Cancer Research
- Synthesis and Biological Evaluation
- Toxin Mechanisms and Immunotoxins
King's College London
2018-2024
The Francis Crick Institute
2018-2023
Guy's Hospital
2020-2023
Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The includes discrete changes in B myelomonocytic cell composition, profoundly altered T phenotypes, selective cytokine/chemokine upregulation SARS-CoV-2-specific...
Abstract Checkpoint inhibition (CPI), particularly that targeting the inhibitory coreceptor programmed cell death protein 1 (PD-1), has transformed oncology. Although CPI can derepress cancer (neo)antigen-specific αβ T cells ordinarily show PD-1-dependent exhaustion, it also be efficacious against cancers evading recognition. In such settings, γδ have been implicated, but functional relevance of PD-1 expression by these is unclear. Here we demonstrate intratumoral TRDV1 transcripts (encoding...
Significance Although gamma delta (γδ) T cells compose an evolutionarily conserved third lineage of diversified lymphocytes, alongside αβ and B cells, they can seem overtly different across species tissues. Thus, human blood γδ show butyrophilin (BTN)3A1-dependent responses to metabolites (“phosphoantigens”) not seen by rodent whereas some rodent, γδ-rich compartments, notably in the skin, lack obvious counterparts. Recently, however, mouse intraepithelial gut were found be regulated...
Butyrophilin (BTN) and butyrophilin-like (BTNL/Btnl) heteromers are major regulators of human mouse γδ T cell subsets, but considerable contention surrounds whether they represent direct receptor (TCR) ligands. We demonstrate that the BTNL3 IgV domain binds directly specifically to a Vγ4+ TCR, "LES" with an affinity (∼15–25 μM) comparable many αβ TCR-peptide histocompatibility complex interactions. Mutations in germline-encoded Vγ4 CDR2 HV4 loops, not somatically recombined CDR3 drastically...
Murine intraepithelial γδ T cells include distinct tissue-protective selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic cell compartment, identifying a diverse repertoire that includes phenotypically subset coexpressing receptor Vγ4 and epithelium-binding integrin CD103. This was disproportionately diminished dysregulated inflammatory bowel disease, whereas on-treatment CD103 + restoration...
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5
Abstract Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because its potential to cause life-threatening Covid-19 disease. By comparison paucisymptomatic clearance by most individuals, been proposed reflect insufficient and/or pathologically exaggerated immune responses. Here we identify consensus peripheral blood signature across 63 hospital-treated patients who were otherwise highly heterogeneous. The core conspicuously blended adaptive B cell responses...
Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at cost broader cell repertoire disruption. We applied genomic DNA-based approach concurrently study the immunoglobulin-heavy (IGH) receptor (TCR) β δ chain loci 95 individuals. Our detected anticipated focusing for IGH repertoire, including expansions clusters related sequences temporally aligned with SARS-CoV-2–specific...
Abstract Antibody-Drug Conjugates (ADCs) developed as a targeted treatment approach to deliver toxins directly cancer cells are one of the fastest growing classes oncology therapeutics, with eight ADCs and two immunotoxins approved for clinical use. However, selection an optimum target payload combination, achieve maximal therapeutic efficacy without excessive toxicity, presents significant challenge. We have platform facilitate rapid cost-effective screening antibody toxin combinations...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
Summary Background Emerging pandemics place immense strains on healthcare systems that may be ameliorated by rapid development of biomarkers whose measurements predict disease severity and additionally inform about causation. Conspicuously, such routine measures rarely include immunological cytokines or chemokines, despite their contributions to host protection immunopathology. Methods Multiplex bead-array ELISA-based serum cytokine chemokine measurements, routinely employed clinical...
Abstract Background α4β7 blockade is a well-established therapy in ulcerative colitis (UC), acting part by preventing lymphocyte ingress into the mucosa. The β7 unit of heterodimer shared α Εβ7, which expressed on both tissue resident memory cells and γδ intra-epithelial lymphocytes (IEL). It was hypothesised that targeting α4- Εβ7 might be more efficacious; however mixed results from phase III studies asks questions biological relevance different Eβ7 expressing cells. Methods Colonic...