Last week, I had the opportunity to listen to and meet Professor Dorothy Crawford. Following an invitation to give a public lecture, Professor Crawford agreed to give, not one, but two lectures – one for the public and one aimed towards a scientific audience. The public lecture was based on her book entitled Deadly Companions: How microbes shaped our history. The scientific lecture was based on how she successfully moved science, particularly immunology, to a cellular therapy.
I have read about Professor Crawford’s pioneering work on cytotoxic T-cell therapy for treating Epstein-Barr virus associated condition entitled post-transplant proliferative disease (references below). Eptein-Barr virus has a special place in my heart because it knows secrets that I am still trying to understand fully – how to immortalise a human B-cell. It is the ability of the virus to immortalise B-cells that causes this post-transplant lymphoma. In order to prevent rejection, patients are immunosuppressed. The immunsuppression allows the outgrowth of Epstein-Barr virus immortalised B-cells which is post tranplant proliferative disease.
Normally the virally immortalised B-cells are controlled by the immune system. Cytotoxic T-cells kill the virally infected cells. This keeps the virus under control in healthy people who have the virus. Most people, including me, live happily with Epstein-Barr virus.
Inspired by this science, which she helped discover, Professor Crawford developed cytotoxic T-cells which could be given to a patient who had an outgrowth of these Epstein-Barr virus immortalised cells. With her team, she developed a bank of these cells, which could be matched to an individual patient and administered safely. These cells were used, in a clinical trail, to treat 33 patients all of whom had progressive disease despite conventional treatment. Their prognosis was poor.
The happy and inspiring result of this trail was that over half of the patients showed a response to the cells and none of the patients showed adverse responses to this novel treatment.
For me, it is inspiring that this was not a custom designed cell from an individual but a bank of cells from helpful blood donors that were tailored to help patients. The approach was based on sound science, it was clever and it was world leading. A new bank of cells that will be capable of supplying cells worldwide is currently being established in Scotland. It is a very worthy next step following this successful trail.
Haque T, McAulay KA, Kelly D, Crawford DH. Allogeneic T-cell therapy for Epstein-Barr virus-positive posttransplant lymphoproliferative disease: long-term follow-up. Transplantation. 2010; 90:93-4.
Haque T, Wilkie GM, Jones MM, Higgins CD, Urquhart G, Wingate P, Burns D, McAulay K, Turner M, Bellamy C, Amlot PL, Kelly D, MacGilchrist A, Gandhi MK, Swerdlow AJ, Crawford DH. Allogeneic cytotoxic T-cell therapy for EBV positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007 Aug 15;110(4):1123-31. Epub 2007 Apr 27. PubMed PMID: 17468341.
Wynn RF, Arkwright PD, Haque T, Gharib MI, Wilkie G, Morton-Jones M, Crawford DH. Treatment of Epstein-Barr-virus-associated primary CNS B cell lymphoma with allogeneic T-cell immunotherapy and stem-cell transplantation. Lancet Oncol. 2005 May;6(5):344-6.
Wilkie GM, Taylor C, Jones MM, Burns DM, Turner M, Kilpatrick D, Amlot PL, Crawford DH, Haque T. Establishment and characterization of a bank of cytotoxic T lymphocytes for immunotherapy of epstein-barr virus-associated diseases. J Immunother. 2004 Jul-Aug;27(4):309-16.
Haque T, Wilkie GM, Taylor C, Amlot PL, Murad P, Iley A, Dombagoda D, Britton KM, Swerdlow AJ, Crawford DH. Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet. 2002 Aug 10;360(9331):436-42.
Haque T, Taylor C, Wilkie GM, Murad P, Amlot PL, Beath S, McKiernan PJ, Crawford DH. Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells. Transplantation. 2001 Oct 27;72(8):1399-402.