A5085737809- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Cancer Research and Treatments
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Immune cells in cancer
Ludwig Cancer Research
2024
University of Oxford
2023-2024
University of Birmingham
2019-2022
Swansea University
2017-2019
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...
Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. activation and downstream effector functions CD4+ CD8+ T-cells are controlled by strength interaction between receptor (TCR) peptides presented human leukocyte antigens (pHLA). The role TCR-pHLA interactions modulating metabolism is unknown. Here first time we explore relative contributions main metabolic pathways functional responses T-cells....
Abstract Metabolic pathways that regulate T-cell function show promise as therapeutic targets in diverse diseases. Here, we at rest cultured human effector memory and central CD4+ T-cells have elevated levels of glycolysis oxidative phosphorylation (OXPHOS), comparison to naïve T-cells. Despite having low resting metabolic rates, naive respond TCR stimulation with robust rapid increases OXPHOS. This early switch requires Akt activity support increased rates STAT5 for amino acid biosynthesis...
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...
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...
Melanoma antigen gene (MAGE)-type antigens are promising targets for cancer immunotherapy as they expressed in cells but not normal tissues, except male germline cells. The mouse P1A shares this MAGE-type expression pattern and has been used a target preclinical tumor models aiming to induce antitumor CD8
Summary Therapeutic cancer vaccines, whether based on neoantigens or shared antigens, will likely be given in the clinic together with standard of care, which often comprises immune checkpoint blockade therapy and chemotherapy. It remains unclear, however, vaccines effectively synergize Here, we tested combination a heterologous prime-boost viral vector vaccine chemotherapy (CarboTaxol) anti-PD- 1. We show that this triple improves tumor control survival different murine models. CarboTaxol,...