Professor Dalgleish is a Professor of Oncology. His work on human retroviruses led to him being a co-discoverer of the fact that HIV used CD4 as a receptor, and senior author of the paper that first linked HIV infection to slim disease in East Africa.
With regard to cancer, Professor Dalgleish has applied the principle of his work in HIV to the immune response to cancer and been involved with many vaccine programmes, mainly against melanoma. Patients on mycobacterium vaccae studies have done far better than expected. Based on these observations, Immodulon has resurrected this vaccine, which is the main vaccine candidate of interest to Professor Dalgliesh's research group.
Nearly all of the group's work on immune response to cancer and the development of vaccines has been funded by the Cancer Vaccine Institute, originally set by families of patients who felt they had benefitted enormously from earlier trials.
The other major line of Professor Dalgliesh's research has been the resurrection of Thalidomide and the development of the analogue programme with Celgene. The first of these, which the group published a phase I/II study on and were surprised to see the strong immune modulatory effect of, was Revlimid. It has subsequently been confirmed, and this agent is now in trial, as an oral adjuvant for vaccines. The drug itself has been outstandingly successful in the clinic for multiple myeloma, while Professor Dalgliesh was awarded the Joshua Lederberg Prize in 2012.
There are many other analogues with good clinical potential, and one of these, Pomalidomide, has also recently been approved. Both agents have marked activity in leukaemias and lymphomas.
His research is focused on three main areas:
1. Development of a therapeutic HIV vaccine, which is now in trial with Bionor Pharma in Norway. There are two specific strains to this - firstly the C5 gp41 immunogen and, secondly, the VAX 4X combined with Revlimid.
2. Development of cancer vaccines immunotherapy. This has involved the resurrection of the Mycobacterium agents, with a focus on obuense, being produced by Immodulon. There are three clinical trials running at present, one in melanoma, a second on a randomised study for pancreatic cancer, and the third on colorectal metastases. The study with UCL in early prostate cancer is being planned.
3. The development of the IMiDs, as well as combinations with other agents and their use as adjuvants for vaccines.
Professor Dalgleish was appointed as foundation chair of oncology at St George’s, University of London in 1991. He graduated MBBS at University College, London, in 1974, having done an intercalated BSc in anatomy with Professor J Z Young, FRS. After training as a general physician and specialist medical oncologist he joined Professor Robin Weiss, then head of the Institute of Cancer Research as a clinical research fellow in 1984. His project was on human retroviruses and he was a co-discoverer of the fact that HIV used CD4 as a receptor and senior author of the paper that first linked HIV infection to slim disease in East Africa.
In 1987 he became a Medical Research Council clinical research fellow at the Northwick Park Clinical Research Centre. Here he continued his work on HIV pathogenesis and became part of an EU group focused on the correlates of immune protection. During this time, the association with the induction of immune activation and disease was shown to be absolute, correlating with the observations in chimpanzees.
Professor Dalgliesh was awarded the Joshua Lederberg Prize in 2012.
Cananzi FC, Mudan S, Dunne M, Belonwu N, Dalgleish AG.Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma. Hum Vaccin Immunother. 2013 Jul 9;9(11).
Liu WM, Scott KA, Thompson M, Dalgleish AG. Dendritic cell phenotype can be improved by certain chemotherapies and is associated with alterations to p21waf1/cip1. Cancer Immunol Immunother. 2013 Jul 4. [Epub ahead of print] PMID:23824498
Fowler DW, Copier J, Dalgleish AG, Bodman-Smith MD. Tripartite immune cell co-operation in the Bacillus Calmette Guérin-induced activation of γδ T cells. Immunol Cell Biol. 2013 Jun 25. doi: 10.1038/icb.2013.30. [Epub ahead of print]PMID:23797069
Henry JY, Labarthe MC, Meyer B, Dasgupta P, Dalgleish AG, Galustian C. Enhanced cross-priming of naive CD8+ T cells by DCs treated by the IMiDs(®) immunomodulatory compounds Lenalidomide and Pomalidomide. Immunology. 2013 Feb 1. PMID:23374145
Ioannou N, Seddon AM, Dalgleish A, Mackintosh D, Modjtahedi H. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC Cancer. 2013 Jan 31;13:41.
Liu WM, Dalgleish AG. Cancer cell-derived supernatants that support the carcinogenic process: a future cancer therapy target? Future Oncol. 2012 Jul;8(7):767-9
Cadogan M, Austen B, Heeney J and Dalgleish A. HLA homology within the C5 domain promotes peptide binding by HIV-1 gp120. AIDS Research and Human Retroviruses. 2008 Jun;24(6):845-55
Clapham P, Weber J, Whitby D, Dalgleish AG, Maddon PJ, Sweet R, Weiss RA. Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells. Nature 1989:337: 368-370
Dalgleish AG, Beverley PCL, Clapham P, Crawford D, Greaves M, Weiss RA. The CD4 (T4) antigen is an essential component of the AIDS virus receptor. Nature 1984:321: 763-767
Serwadda D, Mugerwa RD, Sewankambo NK, Lwegaba A, Carswell JW Kirya GB, Bayley AC, Downing RG, Tedder RS, Clayden SA, Weiss RA, Dalgleish AG. Slim disease: a new disease in Uganda and its association with HTLV-III infection. Lancet ii: 1985:849-853
Evans, C, Morrison, I.Heriot, A. G.Bartlett, J. B.Finlayson, C. Dalgleish, A. G, Kumar, D. The correlation between colorectal cancer rates of proliferation and apoptosis and systemic cytokine levels; plus their influence upon survival. Br J Cancer. 2006. 94(10):1412-9
Dalgleish AG. The relevance of non-linear mathematics (chaos theory) to the treatment of cancer, the role of the immune response and the potential for vaccines. QJM. 1999; 92(6):347-359.
Andrew Gravett PhD - The immunological alteration of cancer cells upon chemotherapeutic treatment
Elwira Kominska PhD - Immunomodulatory role of Apolipoprotein E on monocytes and monocyte-derived dendritic cells
Alan Levatt PhD - An investigation of the effects of novel combinatorial therapies on restoration of gemcitabine sensitivity and anti-tumour immune functions in pancreatic cancer
Rachel Cant PhD - Effects of Low dose Naltrexone on Immune cell function
Emma Sparrow PhD - Does the release of cytolytic granules from gamma-delta T cells contribute to the maturation and migration of dendritic cells?
Dr Wai Liu - Research fellow
Peter L Smith
Helmout Modjtahedi (Kingston University)
Satvinder Mudan (The Royal Marsden)
Farzin Farzeneh (Kings College, London)
Christine Galustian (Kings College, London)
Justin Stebbing (Imperial College, London)
Maja Sommerfelt (Bionor Pharma, Norway)
Birger Sorenson (Bionor Pharma, Norway)
Jerry Zeldis (Celgene)
Dr Alberto Beretta (Instituto Di Ricovero E Cura A Carattere Scientifico. Milan)
Professor Brendon Coventry (University of Adelaide)
Fred Fändrich (University of Schleswig-Holstein, Kiel)
EORTC Melanoma Group
South West London Cancer Network
- Role of HER family members and IGF-IR in the progression of pancreatic cancer and response to therapeutic interventions – co-applicant
Medical Research Council
- Development of cytotopic immunomodulatory agents for targeted localised cancer therapy – Joint lead applicant
Cancer Research UK
- Active surveillance for prostate cancer: embedding a random invitation programme to evaluate novel agents in men following an observational strategy for early prostate cancer
British Research Council
- ‘Vacc-HIV: A novel therapeutic vaccine combination for HIV infection’ co-applicant
Medical Research Council
Over three years, awarded June 2013
- Development of a novel cytotopic immunotherapeutic cocktail for targeted treatment of advanced prostate cancer – co-applicant
Prostate Cancer UK
Awarded Oct 2012
- Role of Canniboids in Glioma
Awarded Sept 2012 - one year
- PhD Studentship - An investigation of the effects of novel combinational therapies on restoration of gemcitabine sensistivity and anti-tumour immune functions in pancreatic cancer
Ralph Bates Pancreatic Research Fund
Awarded October 2010 - 2013
£77,558 over three years
- Combination Therapies of IMiDs in cancer/Exploration of the correct epitopes for a potential HIV vaccine which might prevent disease progression
Awarded 2009 - ongoing
£100,000 per year
- Cancer immunotherapy research
Cancer Vaccine Institute
Awarded 2004 – ongoing
Average £310,000 per year
Professor Dalgleish teaches Biomedical Science special study projects, the Medicine MBBS (graduate entry) course, personal and professional development.
Professor Dalgleish supervises PhD students.