A5039296662- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Cell death mechanisms and regulation
- Adenosine and Purinergic Signaling
- Esophageal Cancer Research and Treatment
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- S100 Proteins and Annexins
- Pancreatic and Hepatic Oncology Research
- Synthesis and Biological Evaluation
University of Southampton
2012-2024
Centre for Cancer Biology
2023
University Hospital Southampton NHS Foundation Trust
2018-2020
Cancer Research UK
2018
Abstract The endoplasmic reticulum aminopeptidase associated with Ag processing, ERAAP, plays an important role in the trimming of antigenic peptides for presentation at cell surface complexed MHC class I molecules. Tumors express varying levels highlighting a possible mechanism immune-evasion through alteration peptide repertoire. Using CT26 tumor model, we investigated effects ERAAP modulation on and use inhibition as antitumor therapy. We show that generation cross-protective GSW11...
Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against has already shown promise in the clinical setting. Conventional plasmid commonly used which together encoded antigen also includes bacterial immunostimulatory CpG motifs target sensor Toll-like receptor 9. Recently vaccines using doggybone (dbDNA™), have been developed without use of bacteria. The cell-free process relies on Phi29 polymerase amplify template followed by protelomerase...
Background CD8 + T cells are a highly diverse population of with distinct phenotypic functions that can influence immunotherapy outcomes. Further insights on the roles specificities and TCR avidity naturally arising tumor-specific cells, where both high low recognizing same peptide-major histocompatibility complex (pMHC) coexist in tumor, crucial for understanding cell exhaustion resistance to PD-1 immunotherapy. Methods CT26 models were treated anti-PD-1 days 3, 6 9 following subcutaneous...
Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour cell responses. In CT26 BALB/c murine model colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ epitopes, AH1 and GSW11, which results an absence detectable IFN-γ-producing GSW11-specific spleen lymph nodes tumour challenged mice. Activation correlates with protection against progression. We wanted examine presence non-functional Treg replete depleted mice, assess...
Abstract Background: The ability to generate potent anti-tumor CTL responses is fundamental the rejection of many tumors. However are suppressed by regulatory T cells (Treg) preventing this. Recent clinical trial studies, using checkpoint inhibitors have shown great promise in inducing protective albeit a minority patients. In mouse CT26 tumor model, removal Treg suppression uncovers cryptic anti-GSW11 CTL, which immunodominant and protective. generation GSW11 peptide ER susceptible...
Abstract Background: Advances in cancer immunotherapy the form of checkpoint blockade such as anti-PD-1, have led to promising results and positive T-cell responses a variety human tumors. However, why some patients respond resulting decrease tumor burden whilst others do not is fully understood. Using murine solid model, which mirrors survival rates seen humans undergoing anti-PD1 treatment, we previously uncovered identified key antigen involved protective cytotoxic anti-tumor response...
T cell avidity plays a crucial role in antigen presentation and influences the quality of TCR signaling metabolic fitness. It is chronic inflammation e.g. cancer where persistent exposure stimulation may lead to exhaustion. Thus, mechanistic insights on roles CD8+ specificities naturally arising tumour-specific cells both high (Tethi) low (Tetlo) recognising same pMHC co-exist tumour, are for understanding resistance PD-1 immunotherapy. CT26 models were treated with anti-PD-1 days 3, 6 9...
Abstract Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour cell responses. In CT26 BALB/c murine model colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ epitopes, AH1 and GSW11, which results an absence detectable IFN-γ producing GSW11- specific spleen lymph nodes tumour challenged mice. Activation GSW11-specific correlates with protection against growth. Here we show that are fact induced Treg-replete, CT26-bearing...