Now showing items 1-20 of 27

    • Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking. 

      Taggart, D; Andreou, T; Scott, KJ; Williams, J; Rippaus, N; Brownlie, RJ; Ilett, EJ; Salmond, RJ; Melcher, A; Lorger, M (2018-02-13)
      Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells results in durable antitumor activity in melanoma patients. Despite high frequency of melanoma ...
    • Antibody-Neutralized Reovirus Is Effective in Oncolytic Virotherapy. 

      Berkeley, RA; Steele, LP; Mulder, AA; van den Wollenberg, DJM; Kottke, TJ; Thompson, J; Coffey, M; Hoeben, RC; Vile, RG; Melcher, A; Ilett, EJ (2018-10)
      Immunotherapy is showing promise for otherwise incurable cancers. Oncolytic viruses (OVs), developed as direct cytotoxic agents, mediate their antitumor effects via activation of the immune system. However, OVs also stimulate ...
    • APOBEC3 Mediates Resistance to Oncolytic Viral Therapy. 

      Huff, AL; Wongthida, P; Kottke, T; Thompson, JM; Driscoll, CB; Schuelke, M; Shim, KG; Harris, RS; Molan, A; Pulido, JS; Selby, PJ; Harrington, KJ; Melcher, A; Evgin, L; Vile, RG (2018-12-21)
      Tumor cells frequently evade applied therapies through the accumulation of genomic mutations and rapid evolution. In the case of oncolytic virotherapy, understanding the mechanisms by which cancer cells develop resistance ...
    • ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment. 

      Dillon, MT; Bergerhoff, KF; Pedersen, M; Whittock, H; Crespo-Rodriguez, E; Patin, EC; Pearson, A; Smith, HG; Paget, JTE; Patel, RR; Foo, S; Bozhanova, G; Ragulan, C; Fontana, E; Desai, K; Wilkins, AC; Sadanandam, A; Melcher, A; McLaughlin, M; Harrington, KJ (2019-06-01)
      PURPOSE: ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the ...
    • CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids. 

      Gonzalez-Exposito, R; Semiannikova, M; Griffiths, B; Khan, K; Barber, LJ; Woolston, A; Spain, G; von Loga, K; Challoner, B; Patel, R; Ranes, M; Swain, A; Thomas, J; Bryant, A; Saffery, C; Fotiadis, N; Guettler, S; Mansfield, D; Melcher, A; Powles, T; Rao, S; Watkins, D; Chau, I; Matthews, N; Wallberg, F; Starling, N; Cunningham, D; Gerlinger, M (2019-04-15)
      BACKGROUND: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high ...
    • Genetically modified lentiviruses that preserve microvascular function protect against late radiation damage in normal tissues. 

      Khan, AA; Paget, JT; McLaughlin, M; Kyula, JN; Wilkinson, MJ; Pencavel, T; Mansfield, D; Roulstone, V; Seth, R; Halle, M; Somaiah, N; Boult, JKR; Robinson, SP; Pandha, HS; Vile, RG; Melcher, AA; Harris, PA; Harrington, KJ (2018-01-24)
      Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy ...
    • Immunogenicity of self tumor associated proteins is enhanced through protein truncation. 

      Kottke, T; Shim, KG; Alonso-Camino, V; Zaidi, S; Maria Diaz, R; Pulido, J; Thompson, J; Rajani, KR; Evgin, L; Ilett, E; Pandha, H; Harrington, K; Selby, P; Melcher, A; Vile, R (2016)
      We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own ...
    • The immunological consequences of radiation-induced DNA damage. 

      Wilkins, AC; Patin, EC; Harrington, KJ; Melcher, AA (2019-04)
      Historically, our understanding of the cytotoxicity of radiation has centred on tumour cell-autonomous mechanisms of cell death. Here, tumour cell death occurs when a threshold number of radiation-induced non-reparable ...
    • Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. 

      Samson, A; Scott, KJ; Taggart, D; West, EJ; Wilson, E; Nuovo, GJ; Thomson, S; Corns, R; Mathew, RK; Fuller, MJ; Kottke, TJ; Thompson, JM; Ilett, EJ; Cockle, JV; van Hille, P; Sivakumar, G; Polson, ES; Turnbull, SJ; Appleton, ES; Migneco, G; Rose, AS; Coffey, MC; Beirne, DA; Collinson, FJ; Ralph, C; Alan Anthoney, D; Twelves, CJ; Furness, AJ; Quezada, SA; Wurdak, H; Errington-Mais, F; Pandha, H; Harrington, KJ; Selby, PJ; Vile, RG; Griffin, SD; Stead, LF; Short, SC; Melcher, AA (2018-01-03)
      Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined ...
    • Oncolytic Herpes Simplex Virus Inhibits Pediatric Brain Tumor Migration and Invasion. 

      Cockle, JV; Brüning-Richardson, A; Scott, KJ; Thompson, J; Kottke, T; Morrison, E; Ismail, A; Carcaboso, AM; Rose, A; Selby, P; Conner, J; Picton, S; Short, S; Vile, R; Melcher, A; Ilett, E (2017-06-16)
      Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumors with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via ...
    • Oncolytic Immunotherapy for Bladder Cancer Using Coxsackie A21 Virus. 

      Annels, NE; Arif, M; Simpson, GR; Denyer, M; Moller-Levet, C; Mansfield, D; Butler, R; Shafren, D; Au, G; Knowles, M; Harrington, K; Vile, R; Melcher, A; Pandha, H (2018-06-29)
      As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) ...
    • Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. 

      Samson, A; Bentham, MJ; Scott, K; Nuovo, G; Bloy, A; Appleton, E; Adair, RA; Dave, R; Peckham-Cooper, A; Toogood, G; Nagamori, S; Coffey, M; Vile, R; Harrington, K; Selby, P; Errington-Mais, F; Melcher, A; Griffin, S (2018-03)
      OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular ...
    • Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. 

      Mansfield, DC; Kyula, JN; Rosenfelder, N; Chao-Chu, J; Kramer-Marek, G; Khan, AA; Roulstone, V; McLaughlin, M; Melcher, AA; Vile, RG; Pandha, HS; Khoo, V; Harrington, KJ (2016-04)
      Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy ...
    • PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma. 

      Smith, HG; Mansfield, D; Roulstone, V; Kyula-Currie, JN; McLaughlin, M; Patel, RR; Bergerhoff, KF; Paget, JT; Dillon, MT; Khan, A; Melcher, A; Thway, K; Harrington, KJ; Hayes, AJ (2019-06-01)
      PURPOSE: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel ...
    • Pembrolizumab in Combination with Radiotherapy for Metastatic Melanoma - Introducing the PERM Trial. 

      Yip, K; Melcher, A; Harrington, K; Illidge, T; Nobes, J; Webster, A; Smith, D; Lorigan, P; Nathan, P; Larkin, J (2018-04)
    • Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer. 

      Annels, NE; Mansfield, D; Arif, M; Ballesteros-Merino, C; Simpson, GR; Denyer, M; Sandhu, SS; Melcher, AA; Harrington, KJ; Davies, B; Au, G; Grose, M; Bagwan, I; Fox, B; Vile, R; Mostafid, H; Shafren, D; Pandha, HS (2019-10-01)
      PURPOSE: The CANON [CAVATAK in NON-muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. PATIENTS AND METHODS: ...
    • A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol. 

      Holyoake, DL; Ward, E; Grose, D; McIntosh, D; Sebag-Montefiore, D; Radhakrishna, G; Patel, N; Silva, M; Mukherjee, S; Strauss, VY; Odondi, L; Fokas, E; Melcher, A; Hawkins, MA (2016-01)
      Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis ...
    • Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21. 

      Müller, LME; Holmes, M; Michael, JL; Scott, GB; West, EJ; Scott, KJ; Parrish, C; Hall, K; Stäble, S; Jennings, VA; Cullen, M; McConnell, S; Langton, C; Tidswell, EL; Shafren, D; Samson, A; Harrington, KJ; Pandha, H; Ralph, C; Kelly, RJ; Cook, G; Melcher, AA; Errington-Mais, F (2019-07-01)
      BACKGROUND: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer ...
    • Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition. 

      Jennings, VA; Scott, GB; Rose, AMS; Scott, KJ; Migneco, G; Keller, B; Reilly, K; Donnelly, O; Peach, H; Dewar, D; Harrington, KJ; Pandha, H; Samson, A; Vile, RG; Melcher, AA; Errington-Mais, F (2019-06-05)
      A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and ...
    • Prime-boost using separate oncolytic viruses in combination with checkpoint blockade improves anti-tumour therapy. 

      Ilett, E; Kottke, T; Thompson, J; Rajani, K; Zaidi, S; Evgin, L; Coffey, M; Ralph, C; Diaz, R; Pandha, H; Harrington, K; Selby, P; Bram, R; Melcher, A; Vile, R (2017-01)
      The anti-tumour effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms, which depend both on the type of virus and the route of delivery. Here, we show that intra-tumoral ...