A5047711932- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Biosimilars and Bioanalytical Methods
- Acute Lymphoblastic Leukemia research
- Viral-associated cancers and disorders
- Cancer-related gene regulation
- Ovarian cancer diagnosis and treatment
- RNA modifications and cancer
- RNA Research and Splicing
- Renal and related cancers
- Genetic factors in colorectal cancer
- Pluripotent Stem Cells Research
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
- T-cell and B-cell Immunology
- Childhood Cancer Survivors' Quality of Life
Queen Mary University of London
2016-2024
Roche (Switzerland)
2021-2024
University of Glasgow
2013-2023
Pfizer (United Kingdom)
2019-2020
Cancer Institute (WIA)
2017-2019
Gartnavel General Hospital
2016
Cancer Research UK Manchester Institute
2016
University of Manchester
2016
Molecular Oncology (United States)
2015
A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)-persistent leukemic stem cells (LSC). These are BCR-ABL1 independent, refractory apoptosis, and serve as a reservoir drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 misregulated in phase CML LSCs. This associated with extensive reprogramming of H3K27me3 targets LSCs, thus sensitizing them apoptosis upon treatment an EZH2-specific...
We are indebted to the patients for donating tumor specimens as part of this study. The authors thank Centre de Ressources Biologiques (CRB)-Sante Rennes (BB-0033-00056) for patient samples, Queen Mary University London Genome Centre for Illumina Miseq sequencing, and support by National Institute Health Research (NIHR) Biomedical at Guy’s St Thomas’ NHS Foundation Trust King’s College London Hiseq sequencing. views expressed are those not necessarily those NHS, NIHR, or Department...
Effective T-cell responses not only require the engagement of receptors (TCRs; "signal 1"), but also availability costimulatory signals ("signal 2"). bispecific antibodies (TCBs) deliver a robust signal 1 by engaging TCR signaling component CD3ε, while simultaneously binding to tumor antigens. The CD20-TCB glofitamab redirects T cells CD20-expressing malignant B cells. Although exhibits strong single-agent efficacy, adding may enhance depth and durability T-cell-mediated cell killing. We...
Abstract Glofitamab, a novel CD20xCD3, T-cell–engaging bispecific antibody, exhibited single-agent activity in Study NP30179, first-in-human, phase 1 trial relapsed/refractory B-cell non-Hodgkin lymphoma. Preclinical studies showed that glofitamab leads to T-cell activation, proliferation, and tumor cell killing upon binding CD20 on malignant cells. Here, we provide evidence of glofitamab’s clinical activity, including pharmacodynamic profile, mode action, factors associated with response,...
Abstract The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis therapy, transitioning from cellular depletion in the leukaemia to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit fate switch cells towards slow-proliferation quiescence, highlighting critical...
Abstract B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception some BCR-ABL1 + patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for B-ALL and chemotherapy remains first-line therapy despite adverse side effects poor efficacy. We show that, although MEK/ERK pathway activated in cells driven by different oncogenes, MEK inhibition does not suppress cell growth....
Background Acute Myeloid leukemia is a heterogeneous disease that requires novel targeted treatment options tailored to the patients’ specific microenvironment and blast phenotype. Methods We characterized bone marrow and/or blood samples of 37 AML patients healthy donors by high dimensional flow cytometry RNA sequencing using computational analysis. In addition, we performed ex vivo ADCC assays allogeneic NK cells isolated from patient material test cytotoxic potential CD25 Mab (also...
Introduction: The antibody-like fusion protein RO7227166 simultaneously targets CD19 on B-cells and 4-1BB (CD137) T cells. activity is strictly dependent crosslinking exhibits no single-agent activity. plus glofitamab shows strong synergy in preclinical models being developed for patients (pts) with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Methods: This first-in-human trial BP41072 (NCT04077723) evaluated the safety, tolerability, pharmacokinetics/dynamics preliminary of...