Photoacoustic imaging for the optimisation of CAR T-cell cancer therapy of soft-tissue tumours - Reporter-gene Studies at Institute of Cancer Research on FindAPhD.com

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Prof Jeff Bamber, Dr Lucia Florescu No more applications being accepted Funded PhD Project (UK Students Only)

London United Kingdom Acoustics Biophysics Cancer Biology Cell Biology Genetics Immunology Molecular Biology

PhD Programmes, Institute of Cancer Research

About the Project

For a full project proposal and details on how to apply using our online recruitment portal please see icr.ac.uk/phds. Please note we only accept applications via the online application system apply.icr.ac.uk

This is one of two projects offered to develop photoacoustic imaging for the optimisation of CAR (chimeric antigen receptor) T-cell cancer therapy. This student will be registered at the Institute of Cancer Research (ICR) in Sutton within the Division of Radiotherapy and Imaging (https://www.icr.ac.uk/our-research/researchdivisions/radiotherapy-and-imaging) but carry out the work in collaboration with the Centre for Vision Speech and Signal Processing at the University of Surrey (https://www.surrey.ac.uk/centre-vision-speech-signal-processing), and will spend at least three months with the National Physical Laboratory (NPL) in Teddington (https://www.npl.co.uk/). Further technical advice will come from iThera Medical (https://www.itheramedical.com/), the company that manufactures the (MSOT™) equipment that will be used for photoacoustic imaging in the project.

In 2018, NHS England and the FDA in the USA approved the availability of CAR T-cell therapy for cancer patients. The therapy involves removal of the patient’s T cells from the blood, followed by their genetic modification to express CARs that specifically target tumour cells, and re-infusion of the cells back into the patient. The access to this “living drug” therapy has set the scene for major development in the field of personalised medicine, with more than 800 CAR T cell therapies being investigated in clinical trials (ClinicalTrials.gov).

Preclinical assessment of the efficacy, pharmacokinetic profile and toxicity profile of CAR T cells is of critical importance in the development and optimisation of such therapies, prior to clinical trials. This is particularly so for application to the treatment solid tumours (Klampatsa et al 2017, Martinez et al 2019, Sacchetti et al 2019). Ideally, this requires an ability to noninvasively image and track the CAR-T cells in vivo. Current imaging approaches (optical, PET, SPECT, MRI) have limitations such as low tissue-penetration depth, poor sensitivity, poor quantification, inadequate resolution, lack of 3D information, or a sensitivity to CAR T cells that fades with time.

The two students will work on related projects which aim to develop and evaluate the use of photoacoustic imaging for determining the biodistribution of the CAR T cells in vivo. Photoacoustic imaging is an exciting relatively new biomedical imaging method which employs an ultrasound scanner in combination with a pulsed laser to create highresolution 3D images of the optical absorption-properties of tissues and cells (Attia et al 2019, Wang and Yao 2016). The CAR T cells will be genetically modified to express proteins that are detectable using photoacoustic imaging. Both projects are multidisciplinary, but the emphasis of this project is in the biological aspects of the new technology development and evaluation, whereas the other project focuses more on the physics and engineering aspects.

1. quantitative cancer imaging biomarkers

2. adoptive cell immunotherapy

3. photoacoustic/optoacoustic/ultrasound imaging

4. reporter gene imaging

5. cell tracking

6. physics/engineering/biology/convergence science PhD London

Funding Notes

Students will receive an annual stipend of £19,000 per annum, as well as having tuition fees and project costs paid for the four-year duration. We are open to applications from eligible UK candidates only.
We particularly welcome applicants from British Black and ethnic minority backgrounds, as they are under-represented at PhD level within the ICR and nationwide.

References

Attia ABE, Balasundaram G, Moothanchery M, Dinish US, Bi R, Ntziachristos V, Olivo M. A review of clinical photoacoustic imaging: Current and future trends. Photoacoustics.16:100144, 2019. ClinicalTrials.gov. https://clinicaltrials.gov/ (2021, accessed 5 February 2021) Klampatsa A, Haas AR, Moon EK, Albelda. Chimeric antigent receptor (CAR) T cell therapy for malignant pleural mesothelioma (MPM). Cancers;0:115, 2017.

Martinez M, Moon EK. CAR T cells for solid tumors: new strategies for finding, inifiltrating and surviving in the tumor microenvironment. Front Immunol;10:128, 2019. Sacchetti B, Botticelli A, Pierelli L, Nuti M, Alimandi M. CAR-T with license to kill solid tumors in search of a winning strategy. Int J Mol Sci;20:1903, 2019. Wang LV, Yao J. A Practical Guide to Photoacoustic Tomography in the Life Sciences. Nat Methods. 28;13:627–638, 2016. Whilding LM, Halim L, Draper B, Parente-Pereira AC, Zabinski T, Davies DM, Maher J. CAR T-cells targeting the integrin αvβ6 and co-expressing the chmokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies. Cancers;11,674, 2019.