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Professor AG Dalgleish

Professor Dalgleish graduated from University College Hospital London having pursued an intercollated BSc with Professor JZ Young, FRS. Following house jobs, he then trained in internal medicine and oncology in Australia, returning to London in 1984 to pursue his interest in viruses, cancer and immunology. He became a Clinical Research Fellow for Professor Robin Weiss, FRS, and made a number of seminal contributions to the world of human retroviruses. He was first author on the paper that discovered that CD4 was the receptor for HIV, as well as senior author on the first paper to link Slim disease in Africa to HIV infection. He also developed an interest in the pathogenesis of how a HTLV-1 causes tropical spastic paraparesis, which is very similar to multiple sclerosis. In 1986 he became a MRC Senior Clinical Scientist and Honorary Consultant Oncologist/Immunologist/General Physician at the Northwick Park Hospital and the Clinical Research Centre. Here he pursued his interest in the pathogenesis of HIV and was one of the first to suggest that the disease was caused by the chronic immune activation induced by the virus and, moreover, proposed with colleagues, the most likely mechanism; that the chronic activation is due to the HLA-like features of the HIV envelope. Professor Dalgleish was involved in early studies with early anti-HIV drugs as well as developing an anti idiotype based vaccine on CD4. He had a large programme grant from Pfizer developing anti retroviral candidates and began to research the anti inflammatory properties of Thalidomide.

In 1991 he was appointed to the Foundation Chair of Oncology, here at St. George's Hospital, and developed an interest in the immune system to treat cancer. He already had previous experience in studies using high dose IL-2 and Interferon and developed an interest in the potential of vaccines to treat cancer. His group demonstrated that allogeneic based vaccines were often as effective, if not more effective, than autologous based vaccines developed a relationship with Dr Donald Morton of the John Wayne Cancer Institute, which saw the melanoma vaccine, based on this principal, being imported into the United Kingdom. Positive phase II studies have led to the largest double blind phase III study in the world, which Professor Dalgleish is the only Principal Investigator in the UK. He developed a similar approach for prostate cancer and was a co-founder of Onyvax, which has recently successfully completed a positive phase II study for hormone resistant prostate cancer patients. He has worked with several vaccine preparations and was one of the first to show the benefits of adding a low dose Interleukin-2 to vaccine schedules.

His interest in Thalidomide led to a collaboration, followed by a programme support from Celgene Corporation. Early work suggested potential benefit for Thalidomide and HIV in cancer and because of the side effect profile of Thalidomide, an analogue programme was commenced. One of these analogues, which was researched and first tested on solid tumours here at St. George's, has been shown to be one of the most active treatments for multiple myeloma and is being developed for this indication. Another anologue, which we have published on, is even more active in myeloma and is the subject of our current research programme. Professor Dalgleish's main research interest at present involves the use of dendritic cells to optimise the development of cancer vaccines. This is supported by programme level support from the Cancer Vaccine Institute and The Fischer Family Trust. These are the main focus of clinical studies.

Current clinical trials include collaboration with the EORTC as well as several phase I/II studies developed internally.

Professor Dalgleish has held grants from all the major funding agencies and is on the Grant Committee for Cancer Projects at the European Commission. He is on the Editorial Board of all major journals, as well as several review publications. He has published over two hundred and sixty peer reviewed publications, including in Nature Cells, Science, Cancer Research, Journal of Immunology, British Journal of Cancer, etc., and has co-edited four text books as well as contributing over forty chapters.

Some of Professor Dalgleish's papers are as follows:

  • Dalgleish AG. Cancer and Inflammation. Br. J. Cancer. 2005 Feb28;92(4):792-3.
  • Bartlett JB, Michael A, Clarke IA, Dredge K, Nicholson S, Kristeleit, H, Polychronis A, Pandha H, Muller GW, Stirling DI, Zeldis J, Dalgleish AG. Phase 1 study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. British Journal of Cancer 2004(90);955-961.
  • Pandha HS, John RJ, Hutchinson J, James N, Whelan M, Corbishley C, Dalgleish AG. Dendritic cell immunotherapy for urological cancers using cryopreserved allogeneic tumour lysat-pulsed cells: a phase I/II study. BJU Int. 2004 Aug:94(3):412-8.
  • Schey, SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, Streetly M, Dalgleish AG. Phase I study of an immunomodulatory thalidomide analog, CC-4047, in relapsed or refractory multiple myeloma. J Clin Oncol. 2004 Aug 15,22(16):3269-76.
  • Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its ImiD derivatives as anticancer agents. Nat Rev Cancer. 2004 Apr:4(4):314-22.
  • Marriott JB, Clarke IA, Czajka A, Dredge K, Childs K, Man HW, Schafer P, Grovinda S, Muller GW, Stirling DI, Dalgleish AG. A novel subclass of thalidomide analogue with anti-solid tumor activity which caspase-dependent apoptosis is associated with altered expression Bcl-2 family proteins. Cancer Res. 2003:1:63(3):593-9.
  • Nicholson S, Guile K, John J, Clarke IA, Diffley J, Donnellan P, Michael A, Szlosarek P, Dalgleish AG. A randomized phase II trial of SRL172 (Mycobacterium vaccae)+/- low-dose interleukin-2 in the treatment of metastatic malignant melanoma. Melanoma Res. 2003 Aug:13(14);389-93.
  • John J, Hutchinson J, Dalgleish A & Pandha H. Cryopreservation of immature monocyte-derived dendritic cells results in enhanced cell maturation but reduced endocytic activity and efficiency of adenoviral transduction. J Immunol Methods. (2003) 272, 35-48.
  • Dredge K, Marriott JB, Todryk SM, Muller GW, Chen R, Stirling DI & Dalgleish, AG Protective antitumour immunity induced by a Costimulatory Thalidomide Analog in Conjunction with Whole Tumour Cell Vaccination is Mediated by Increased Th1-type Immunity. J Immunol. (2002) 16, 4914-9.
  • O'Byrne KJ & Dalgleish AG Chronic Immune Activation and Inflammation as the Cause of Malignancy Br J Cancer (2001). 85, 473-83.

Others, please see PubMed.