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Characterisation and preclinical evaluation of a fibroblast-activating protein (FAP) targeted TRUCK CAR T-cell therapy for malignant pleural mesothelioma (MPM)

  • Full or part time
    Dr A Klampatsa
    Prof A Melcher
    Prof C Isacke
  • Application Deadline
    Sunday, November 17, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes. We are committed to attracting and developing the best minds in the world to join us in our mission—to make the discoveries that defeat cancer.

Characterisation and preclinical evaluation of a fibroblast-activating protein (FAP) targeted TRUCK CAR T-cell therapy for malignant pleural mesothelioma (MPM)

Project Description:
Malignant mesothelioma (MM) is a highly lethal and incurable malignancy involving the body’s mesothelial surfaces, mainly the pleura. Chimeric Antigen Receptors (CARs) are membrane-spanning fusion receptors composed of a targeting moiety, which binds directly to tumour-associated antigens (TAAs), as well as co-signalling intracellular domains that allow activation and effector function when these CARs are engineered into T cells. Despite CAR T cell therapy successes in blood malignancies, their use in solid malignancies, including MM, is more challenging, partly due to the immunosuppressive tumour microenvironment (TME).
In this PhD project, the student will characterize and test an augmented CAR T cell therapy approach by using what has been termed a “TRUCK (T-Cell-Redirected for Universal Cytokine Killing)” with the aim to both target an antigen (the fibroblast-activating protein FAP, found in cancer-associated fibroblasts) and deliver a cargo (TGF-beta blocking peptides) to the tumour at the same time. Evaluation of efficacy of the developed TRUCK CAR product with be done in relevant in vitro (cell lines, 3D spheroids) and in vivo (syngeneic and immunocompromised) tumour model. Combination treatments of the TRUCK CAR with checkpoint inhibitors will also be evaluated in vivo. The project aims to test whether this double-targeting strategy will render CAR T cells more efficacious within the tumour microenvironment, ultimately augmenting the therapeutic effect of this therapy in mesothelioma.

Keywords /Subject Areas:
Immunotherapy
CAR T cell
Mesothelioma
Tumour microenvironment

Funding Notes

Students receive an annual stipend, currently £21,000 per annum, as well as having tuition fees (both UK/EU and overseas) and project costs paid for the four-year duration. We are open to applications from any eligible candidates and are committed to attracting and developing the best minds in the world.
See icr.ac.uk/phds to apply
Applications close 11:55pm UK time on Sunday 17th November 2019

Candidates must have a first class or upper second class honours BSc Honours/MSc in Cancer, Cell or Molecular Biology, or Immunology.



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