Following completion of his BSc (hons) in biochemistry at the University of Aberdeen, Alistair undertook his PhD in stem cell biology at the University of Edinburgh’s Institute for Stem Cell Research. Here, he studied the embryonic origins of the thymus – a key organ in adaptive immune system development. He joined NCARD in 2011, where he has been heavily involved with clinical trials of immunotherapy in mesothelioma. Immunotherapy can work well, but unfortunately for less than half of patients who receive it; Alistair’s work has focussed around looking for immune ‘biomarkers’ i.e. detectable signatures in the blood that may indicate whether a patient is likely to have a good response to the treatment. More recently, he has instigated a research program attempting to use radiotherapy as a tool to improve the likelihood of successful anti-tumour immunotherapy.
Dr Alistair Cook
DR ALISTAIR COOK
SENIOR RESEARCH FELLOW
BSC ABERD., PHD EDIN
In a recently completed clinical trial testing the combination of chemotherapy and a type of immunotherapy, known as ‘checkpoint blockade’, to treat malignant mesothelioma, we collected blood and tissue samples from over 50 participants. Because the trial worked well, our team will now do a series of studies to see if we can predict which patients got the most benefit. We are looking at gene expression in tumours (both at the bulk tissue and single-cell level), DNA mutations, and examining changes in the type and function of immune cells both in blood and inside the tumour. We have received funds from a number of sources to analyse these samples:
- Anagnostou V, Nowak AK, Forde P, Cook AM, Lesterhuis JL, Brahmer J, Scharpf R, Velculescu V, Smith K, Molecular Mechanisms of Response and Resistance to Immunotherapy in Mesothelioma. US$ 258,047 (2020-2024) US Department of Defense; Team Award.
- Nowak AK, Lesterhuis JW, Forrest A, Cook AM. Using gene expression to predict successful responses to chemoimmunotherapy. US$ 98,448.00 (2019-2021) Mesothelioma Applied Research Foundation.
- Nowak AK, Cook AM, Lesterhuis JW. Using single-cell PCR to predict responses to chemo-immunotherapy – a pilot study. In-kind funding to analyse 6 patient samples. (2019-2020)
- Nowak AK, Lesterhuis WJ, Lassmann T, Cook AM, Yip S, McDonnell AM. Laboratory tests to understand why some patients with mesothelioma respond better to a combination of chemotherapy and immunotherapy. $99,876.00 (2019-2020) Cancer Council of Western Australia.
Checkpoint blockade immunotherapy has been used to treat a growing number of cancer types. It can work amazingly well for some people, and not at all for others. There is evidence that radiotherapy may be a useful tool to increase the proportion of people who benefit, and we have received funding from both the Cancer Council of WA and Cancer Australia to help us understand the best way to combine these to treatments:
- Ebert M, Cook AM, Nowak AK, Gill S, Jeraj R, McDonnell AM. Optimising the combination of radiotherapy and immunotherapy for cancer therapy. $98,632.06 (2019-2020) Cancer Council of Western Australia.
- Ebert M, Cook AM, Nowak AK, Gill S, Jeraj R. Mixed radiotherapy fractionation: modulating tumour microenvironment to stimulate and enhance immunotherapy. $597,521 (2019-2022) Cancer Australia.
- Nowak AK, Lake RA, Robinson BWS, Lesterhuis WJ, Waithman J, Cook AM, McDonnell AM. The abscopal effect of radiotherapy in the context of checkpoint blockade in a mouse thoracic cancer model. $97,103.00 (2016) Cancer Council Western Australia.
- PhD candidate Synat Keam was awarded the Peter Douglas Swift scholarship for studies into mesothelioma.
- PhD candidate Wes Wilson was awarded a Young Investigator travel award for the International Mesothelioma Interest Group (IMIG) conference.
- Nowak AK, Brosseau S, Cook AM, Zalcman G. Antiangiogenesis strategies in mesothelioma. Frontiers in oncology. 2020. DOI: 10.3389/fonc.2020.00126. PMID: 32133285
- Aston WJ, Hope DE, Cook AM, Boon L, Dick I, Nowak AK, Lake RA, Lesterhuis WJ. Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment. Oncoimmunology. 2019. DOI: 10.1080/2162402X.2019.1641390. PMID: 31646089
- Nowak AK, McDonnell AM, Cook AM. Immune checkpoint inhibition for the treatment of mesothelioma, Expert Opinion on Biological Therapy. 2019. DOI: 10.1080/14712598.2019.1606209. PMID: 31046484
- Chee J, Watson MW, Chopra A, Nguyen B, Cook AM, Creaney J, Lesterhuis WJ, Robinson BW, Lee YCG, Nowak AK, Lake RA, McDonnell AM. Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors. BMC Research Notes. 2018; 11:864. DOI: 10.1186/s13104-018-3953-x. PMID: 30518402
- Cook A, McDonnell A, Robinson BWS, Lake RA, Nowak AK. Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters. BMC Cancer. 2017; 17:417. DOI: 10.1186/s12885-017-3403-5. PMID: 28619093
- Ulyachenko S, O’Neill KE, Medley T, Farley AM, Vaidya HJ, Cook AM, et al. Identification of a bipotent epithelial progenitor population in the adult thymus. Cell Reports. 2016; 14(12):2819-32. doi: 10.1016/j.celrep.2016.02.080. PMID: 26997270
- Cook A, Lesterhuis WJ, Nowak AK, Lake RA. Chemotherapy and immunotherapy: Mapping the road ahead. Current Opinion in Immunology. 2016; 39:23-9. DOI: 10.1016/j.coi.2015.12.003. PMID: 26724433