Immunotherapies have changed the paradigm of cancer treatment away from conventional cytotoxic chemotherapy. However, immunotherapy outcomes remain more limited in acute myeloid leukaemia (AML) than in other settings, e.g., acute lymphoblastic leukaemia. This may partly be due to a highly immunosuppressive tumour microenvironment (TME), allowing AML to survive undisturbed. Doctors are therefore developing approaches to treat the patient’s immune system with drugs enabling it to destroy the cancer. This new branch of medicine is called immuno-oncology and, though still in its early days, it is saving lives. However, this approach doesn’t always work for every patient. It is therefore crucial to determine which patients are likely to respond and which aren’t. We have previously shown that AML cells evade the immune system and that their genetic “make-up” can help clinicians predict response to chemotherapy, a direct form of attack on rapidly dividing cancer cells, and to immunotherapy with an antibody marking AML cells for destruction by “killer” immune cells.
Natural killer (NK) cells are an emerging therapy for patients with haematological and solid tumors. Wugen is a clinical-stage biotechnology company headquartered in St. Louis, USA, who is leveraging its proprietary Moneta™ platform and deep genomic engineering expertise to pioneer a new class of memory NK cell therapies to treat haematological and solid tumour malignancies (www.wugen.com).
While adoptive cell therapies have proven a powerful tool against hematological cancers, their application to solid tumours has historically been limited by restricted cell trafficking to tumours and by the harsh TME. NK cell therapy products being developed at Wugen originate from healthy donors, are further manipulated in order to enhance their function to destroy cancer cells, even in a hostile TME, and address the needs of patients with solid tumors, acute myeloid leukaemia (AML) and T-cell malignancies.
This is a truly unique opportunity for the successful candidate to work alongside established academics and accomplished partners from Wugen with the aim to characterise the molecular and functional features of a “memory” NK-cell immunotherapy product currently in clinical development. They will have access to state-of-the-art omics platforms and will collect transcriptomic, proteomic, metabolomic and functional data from NK cells. They will leverage advanced computational biology approaches to integrate this information and to generate knowledge that will advance NK cells as a commercially scalable, off-the-shelf therapy for cancer.
The post-graduate researcher will be based in Nottingham Trent University’s John van Geest Cancer Research Centre and is expected to travel internationally to spend some time at Wugen USA as part of their PhD training.
Rutella S, Vadakekolathu J, Mazziotta F, et al. Signatures of immune senescence predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia. Journal of Clinical Investigation 2022; 132 (21): e159579. DOI: 10.1172/JCI159579.
Uy GL, Aldoss I, Foster MC, et al. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood 2021; 137 (6): 751–762. DOI: 10.1182/blood.2020007732.
Vadakekolathu J, Minden MD, Hood T, et al. Immune landscapes predict therapeutic resistance, immunotherapy response and clinical outcomes in acute myeloid leukemia. Science Translational Medicine 2020; 12 (Issue 546): eaaz0463. DOI: 10.1126/scitranslmed.aaz0463.
Romee R, Rosario M, Berrien-Elliott MM, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Science Translational Medicine 2016; 8 (Issue 357): 357ra123. DOI: 10.1126/scitranslmed.aaf2341.
Entrants must have solid foundational knowledge of immunology and how the immune response is subverted in individuals who have cancer. Experience of statistics and bioinformatics, as well as a good understanding of molecular characterisation techniques such as genomics, transcriptomics or proteomics are desirable.
How to apply
Please visit our how to apply page for a step-by-step guide and make an application.
Application deadline: Saturday 30 September 2023.
Fees and funding
This is a match fund project supported by Wugen (https://www.wugen.com/about-us/).
Guidance and support
Find out about guidance and support for PhD students.