Now showing items 1-20 of 39

    • 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)
      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)
      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 ...
    • APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy. 

      Driscoll, CB; Schuelke, MR; Kottke, T; Thompson, JM; Wongthida, P; Tonne, JM; Huff, AL; Miller, A; Shim, KG; Molan, A; Wetmore, C; Selby, P; Samson, A; Harrington, K; Pandha, H; Melcher, A; Pulido, JS; Harris, R; Evgin, L; Vile, RG (2020-02-07)
      APOBEC3B, an anti-viral cytidine deaminase which induces DNA mutations, has been implicated as a mediator of cancer evolution and therapeutic resistance. Mutational plasticity also drives generation of neoepitopes, which ...
    • 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)
      <h4>Purpose</h4>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 ...
    • 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)
      <h4>Background</h4>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 ...
    • Combination therapy with oncolytic viruses and immune checkpoint inhibitors. 

      Chiu, M; Armstrong, EJL; Jennings, V; Foo, S; Crespo-Rodriguez, E; Bozhanova, G; Patin, EC; McLaughlin, M; Mansfield, D; Baker, G; Grove, L; Pedersen, M; Kyula, J; Roulstone, V; Wilkins, A; McDonald, F; Harrington, K; Melcher, A (2020-06)
      <b>Introduction</b>: Immune checkpoint inhibitors (ICI) have dramatically improved the outcome for cancer patients across multiple tumor types. However the response rates to ICI monotherapy remain relatively low, in part ...
    • Combination Therapy With Reovirus and Anti-PD-1 Blockade Controls Tumor Growth Through Innate and Adaptive Immune Responses. 

      Rajani, K; Parrish, C; Kottke, T; Thompson, J; Zaidi, S; Ilett, L; Shim, KG; Diaz, R-M; Pandha, H; Harrington, K; Coffey, M; Melcher, A; Vile, R (2016-02)
      Oncolytic reovirus can be delivered both systemically and intratumorally, in both preclinical models and in early phase clinical trials. Reovirus has direct oncolytic activity against a variety of tumor types and antitumor ...
    • Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer. 

      Crespo-Rodriguez, E; Bergerhoff, K; Bozhanova, G; Foo, S; Patin, EC; Whittock, H; Buus, R; Haider, S; Muirhead, G; Thway, K; Newbold, K; Coffin, RS; Vile, RG; Kim, D; McLaughlin, M; Melcher, AA; Harrington, KJ; Pedersen, M (2020-08)
      <h4>Background</h4>The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although ...
    • Computational Image Analysis of T-Cell Infiltrates in Resectable Gastric Cancer: Association with Survival and Molecular Subtypes. 

      Challoner, BR; von Loga, K; Woolston, A; Griffiths, B; Sivamanoharan, N; Semiannikova, M; Newey, A; Barber, LJ; Mansfield, D; Hewitt, LC; Saito, Y; Davarzani, N; Starling, N; Melcher, A; Grabsch, HI; Gerlinger, M (2021-01)
      <h4>Background</h4>Gastric and gastro-esophageal junction cancers (GCs) frequently recur after resection, but markers to predict recurrence risk are missing. T-cell infiltrates have been validated as prognostic markers in ...
    • Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. 

      Galluzzi, L; Vitale, I; Warren, S; Adjemian, S; Agostinis, P; Martinez, AB; Chan, TA; Coukos, G; Demaria, S; Deutsch, E; Draganov, D; Edelson, RL; Formenti, SC; Fucikova, J; Gabriele, L; Gaipl, US; Gameiro, SR; Garg, AD; Golden, E; Han, J; Harrington, KJ; Hemminki, A; Hodge, JW; Hossain, DMS; Illidge, T; Karin, M; Kaufman, HL; Kepp, O; Kroemer, G; Lasarte, JJ; Loi, S; Lotze, MT; Manic, G; Merghoub, T; Melcher, AA; Mossman, KL; Prosper, F; Rekdal, Ø; Rescigno, M; Riganti, C; Sistigu, A; Smyth, MJ; Spisek, R; Stagg, J; Strauss, BE; Tang, D; Tatsuno, K; van Gool, SW; Vandenabeele, P; Yamazaki, T; Zamarin, D; Zitvogel, L; Cesano, A; Marincola, FM (2020-03)
      Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple ...
    • Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma. 

      Close, HJ; Stead, LF; Nsengimana, J; Reilly, KA; Droop, A; Wurdak, H; Mathew, RK; Corns, R; Newton-Bishop, J; Melcher, AA; Short, SC; Cook, GP; Wilson, EB (2020-04)
      Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination ...
    • 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)
      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 ...
    • Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours. 

      Young, K; Lawlor, RT; Ragulan, C; Patil, Y; Mafficini, A; Bersani, S; Antonello, D; Mansfield, D; Cingarlini, S; Landoni, L; Pea, A; Luchini, C; Piredda, L; Kannan, N; Nyamundanda, G; Morganstein, D; Chau, I; Wiedenmann, B; Milella, M; Melcher, A; Cunningham, D; Starling, N; Scarpa, A; Sadanandam, A (2020-09-03)
      <h4>Objective</h4>A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to ...
    • 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 (2016-01)
      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 ...
    • Inflammatory microenvironment remodelling by tumour cells after radiotherapy. 

      McLaughlin, M; Patin, EC; Pedersen, M; Wilkins, A; Dillon, MT; Melcher, AA; Harrington, KJ (2020-04)
      The development of immune checkpoint inhibitors (ICIs) is revolutionizing the way we think about cancer treatment. Even so, for most types of cancer, only a minority of patients currently benefit from ICI therapies. Intrinsic ...
    • 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)
      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 ...
    • Looking a Gift Horse in the Mouth: Observations on NHS England's Interim Guidance on Pembrolizumab in Head and Neck Squamous Cell Cancer. 

      Harrington, KJ; Bhide, SA; Forster, MD; Good, JS; Gunn, L; Kong, A; Melcher, AA; Metcalf, R; Nenclares, P; Newbold, KL; Nutting, CM; Prestwich, R; Sacco, JJ; Soliman, H; Wong, KH (2020-08)
    • 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)
      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 ...