A5103147157- Virus-based gene therapy research
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Growth Hormone and Insulin-like Growth Factors
- Phagocytosis and Immune Regulation
- Bone health and treatments
- Bone health and osteoporosis research
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
University of Oxford
2017-2021
German Cancer Research Center
2015-2016
Heidelberg University
2015-2016
St James's University Hospital
2000
Lincoln County Hospital
2000
Glasgow Royal Infirmary
1989
The problem Osteoporotic fractures are a major public health problem.It has been estimated that in the USA remaining lifetime fracture risk at age of 50 years is 40% for white women and 13% men, 1 sites being spine, forearm hip.This results considerable morbidity mortality rising costs, including acute hospital care long term home or nursing home.The total annual cost osteoporotic England Wales £742 million ($464 million). 2These costs likely to increase as population ages. Screening BONE...
Abstract Effective immunotherapy of stromal-rich tumors requires simultaneous targeting cancer cells and immunosuppressive elements the microenvironment. Here, we modified oncolytic group B adenovirus enadenotucirev to express a stroma-targeted bispecific T-cell engager (BiTE). This BiTE bound fibroblast activation protein on cancer-associated fibroblasts (CAF) CD3ϵ T cells, leading potent death. Treatment fresh clinical biopsies, including malignant ascites solid prostate tissue, with...
Abstract Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus infect nearby cells and repeat process. We modified oncolytic group B adenovirus EnAdenotucirev (EnAd) express a bispecific single‐chain antibody, secreted from infected tumour into microenvironment. This T‐cell engager (Bi TE ) binds Ep CAM on target cross‐links them CD 3 T cells, leading clustering activation of both 4 8 cells. Bi transcription can be controlled by major...
Tumour-associated macrophages (TAMs) are often implicated in cancer progression but can also exert anti-tumour activities. Selective eradication of cancer-promoting (M2-like) TAM subsets is a highly sought-after goal. Here, we have devised novel strategy to achieve selective depletion, involving the use T cell engagers direct endogenous cytotoxicity towards specific M2-like TAMs. To avoid "on-target off-tumour" toxicities, explored localising expression tumour with enadenotucirev (EnAd), an...
Background Programmed death-ligand 1 (PD-L1) is an important immune checkpoint protein that can be regarded as a pan-cancer antigen expressed by multiple different cell types within the tumor. While antagonizing PD-L1 well known to relieve PD-1/PD-L1-mediated T suppression, here we have combined this approach with immunotherapy strategy target cytotoxicity directly toward PD-L1-expressing cells. We developed bi-specific engager (BiTE) crosslinking and CD3ε demonstrated targeted using...
Abstract Tumor cells exhibiting the Warburg effect rely on aerobic glycolysis for ATP production and have a notable addiction to anaplerotic use of glutamine macromolecular synthesis. This strategy maximizes cellular biosynthetic potential while avoiding excessive depletion NAD+ provides an attractive anabolic environment viral infection. Here, we evaluate infection highly permissive poorly cancer with wild-type adenoviruses oncolytic chimeric adenovirus enadenotucirev (EnAd). All caused...
<div>Abstract<p>Effective immunotherapy of stromal-rich tumors requires simultaneous targeting cancer cells and immunosuppressive elements the microenvironment. Here, we modified oncolytic group B adenovirus enadenotucirev to express a stroma-targeted bispecific T-cell engager (BiTE). This BiTE bound fibroblast activation protein on cancer-associated fibroblasts (CAF) CD3ϵ T cells, leading potent death. Treatment fresh clinical biopsies, including malignant ascites solid prostate...
<p>Time-lapse sequence of EnAd-CMV-FAPBiTE-mediated cytotoxicity DLD and NHDF cells.</p>
<p>Time-lapse sequence of EnAd-mediated cytotoxicity DLD cells.</p>
<p>Supplementary Files detailing additional experiments supporting the conclusions of manuscript, including activation, cytotoxicity, and cytokine analyses. Supplementary tables contain more details on characterisation patient biopsies virus stocks used in study.</p>
<p>Time-lapse sequence of uninfected control cultures DLD, NHDF, and T cells.</p>
<p>Time-lapse sequence of uninfected control cultures DLD, NHDF, and T cells.</p>
<p>Time-lapse sequence of EnAd-CMV-FAPBiTE-mediated cytotoxicity DLD and NHDF cells.</p>
<p>Supplementary Files detailing additional experiments supporting the conclusions of manuscript, including activation, cytotoxicity, and cytokine analyses. Supplementary tables contain more details on characterisation patient biopsies virus stocks used in study.</p>
<p>Time-lapse sequence of EnAd-mediated cytotoxicity DLD cells.</p>
<div>Abstract<p>Effective immunotherapy of stromal-rich tumors requires simultaneous targeting cancer cells and immunosuppressive elements the microenvironment. Here, we modified oncolytic group B adenovirus enadenotucirev to express a stroma-targeted bispecific T-cell engager (BiTE). This BiTE bound fibroblast activation protein on cancer-associated fibroblasts (CAF) CD3ϵ T cells, leading potent death. Treatment fresh clinical biopsies, including malignant ascites solid prostate...