A5060431616- Neuroblastoma Research and Treatments
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Immune cells in cancer
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Endoplasmic Reticulum Stress and Disease
- Neutropenia and Cancer Infections
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- Aldose Reductase and Taurine
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
University of Birmingham
2016-2024
Newcastle University
2014
BackgroundTargeting of MDSCs is a major clinical challenge in the era immunotherapy. Antibodies which deplete murine models can reactivate T cell responses. In humans such approaches have not developed due to difficulties identifying targets amenable translation.MethodsRNA-sequencing M-MDSCs and G-MDSCs from cancer patients was undertaken. Flow cytometry immunohistochemistry blood tumours determined MDSC CD33 expression. were treated with Gemtuzumab ozogamicin internalisation kinetics, death...
Therapeutic approaches which aim to target Acute Myeloid Leukaemia through enhancement of patients' immune responses have demonstrated limited efficacy date, despite encouraging preclinical data. Examination AML patients treated with azacitidine (AZA) and vorinostat (VOR) in a Phase II trial, an increase the expression Cancer-Testis Antigens (MAGE, RAGE, LAGE, SSX2 TRAG3) on blasts that these can be recognised by circulating antigen-specific T cells. Although cells potential activated...
Background The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role the pathophysiology of number pediatric cancers. We report first child study recombinant human arginase, BCT-100, hematological, solid or CNS Procedure PARC was single arm, Phase I/II, international, open label study. BCT-100 given intravenously over one hour at weekly intervals. I section utilized modified 3 + design where...
Neuroblastoma is the most common childhood solid tumor, yet prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)-dependent uptake
Cancer cells take up amino acids from the extracellular space to drive cell proliferation and viability. Similar mechanisms are applied by immune cells, resulting in competition between conventional T or indeed chimeric antigen receptor (CAR) tumor for limited availability of within environment. We demonstrate that can be re-engineered express SLC7A5 SLC7A11 transmembrane acid transporters alongside CARs. Transporter modifications increase CAR T-cell under low tryptophan cystine conditions...
Recombinant granulocyte colony-stimulating factor (G-CSF) is frequently administered to patients with cancer enhance recovery post-chemotherapy. Clinical trials have also used G-CSF modulate myeloid cell function in pregnancy and inflammatory diseases. Although the contribution of expanding normal granulocytes well known, effect this cytokine on phenotype immunosuppressive granulocytic cells remains unclear. Here, we investigate impact physiological iatrogenic an as yet undescribed ensuing...
Acute myeloid leukaemia (AML) creates an immunosuppressive environment to conventional T cells through Arginase 2 (ARG2)-induced arginine depletion. We identify that AML blasts release the acute phase protein serum amyloid A (SAA), which acts in autocrine manner upregulate ARG2 expression and activity, promote blast viability. Following vitro cross-talk invariant natural killer (iNKT) become activated, mitochondrial capacity, IFN-γ. iNKT retain their ability proliferate be activated despite...
Downstream of activating transcription factor 4 (ATF‐4) in Caco‐2 cells response to stress. In the present study we show that increased expression GlyT‐1a gene following stress is dependent on elements contained within 5’untranslated region (UTR). transfected with plasmid constructs containing sequences representative proximal promoter and 5’UTR upstream a beta‐galactosidase reporter showed activity treatment thapsigargin (Tg), tunicamycin (Tu), amino acid (AA) starvation,...
<div>Abstract<p>Neuroblastoma is the most common childhood solid tumor, yet prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)–dependent uptake <i>in vitro</i> or therapeutic depletion pegylated recombinant BCT-100, significantly delayed tumor development and prolonged...
<p>Supplementary Figure 3 Neuroblastoma conditioning upregulates IL-1ï�¢ï€ and TNF-ï�¡ï€ expression in macrophages</p>
<p>Supplementary Figure 4 Macrophage infiltration and downstream effects on neuroblastoma tumours</p>
<p>Supplementary Figure 2 Cytokine profile of tumour induced macrophages or granulocytes</p>
<p>Supplementary Figure Legends and Tables</p>
<p>Supplementary Figure 5 : IL-1ï�¢ï€ and TNF-ï�¡ï€ drive neuroblastoma cell proliferation</p>
<p>Supplementary Figure 1: M1-Macrophage infiltrate neuroblastoma</p>
<p>Supplementary Figure 5 : IL-1ï�¢ï€ and TNF-ï�¡ï€ drive neuroblastoma cell proliferation</p>
<p>Supplementary Figure 3 Neuroblastoma conditioning upregulates IL-1ï�¢ï€ and TNF-ï�¡ï€ expression in macrophages</p>
<p>Supplementary Figure 4 Macrophage infiltration and downstream effects on neuroblastoma tumours</p>
<p>Supplementary Materials and Methods CLEAN version</p>
<p>Supplementary Figure 2 Cytokine profile of tumour induced macrophages or granulocytes</p>
<p>Supplementary Figure 1: M1-Macrophage infiltrate neuroblastoma</p>