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Full-Text Articles in Medicine and Health Sciences
Small Molecules That Inhibit Tnf Signalling By Stabilising An Asymmetric Form Of The Trimer, James O'Connell, John Porter, Boris Kroeplien, Tim Norman, Stephen Rapecki, Rachel E. Davis, David Mcmillan, Tracy Arakaki, Alex Burgin, David Fox Iii, Tom Ceska, Fabien Lecomte, Alison Maloney, Alex Vugler, Bruce Carrington, Benjamin P. Cossins, Tim Bourne, Alastair Lawson
Small Molecules That Inhibit Tnf Signalling By Stabilising An Asymmetric Form Of The Trimer, James O'Connell, John Porter, Boris Kroeplien, Tim Norman, Stephen Rapecki, Rachel E. Davis, David Mcmillan, Tracy Arakaki, Alex Burgin, David Fox Iii, Tom Ceska, Fabien Lecomte, Alison Maloney, Alex Vugler, Bruce Carrington, Benjamin P. Cossins, Tim Bourne, Alastair Lawson
Faculty Publications
Tumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn's disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for …
Virus-Specific Memory T Cells Populate Tumors And Can Be Repurposed For Tumor Immunotherapy, Pamela C. Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E. Nelson, Rachel Davis, Luke S. Manlove, Christopher A. Pennell, Bruce R. Blazar, Clark C. Chen, Melissa A. Geller, Vaiva Vezys, David Masopust
Virus-Specific Memory T Cells Populate Tumors And Can Be Repurposed For Tumor Immunotherapy, Pamela C. Rosato, Sathi Wijeyesinghe, J Michael Stolley, Christine E. Nelson, Rachel Davis, Luke S. Manlove, Christopher A. Pennell, Bruce R. Blazar, Clark C. Chen, Melissa A. Geller, Vaiva Vezys, David Masopust
Faculty Publications
The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural …