UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Little Princess Trust PhD Studentship in the Childhood Brain Tumour Research Group

Enhancing CAR T-cell expansion and prolonged persistence for the effective treatment of paediatric medulloblastoma


1. We hypothesise that IL13RA2 can be leveraged as a safe and effective CART therapy against group3 MB

2. We hypothesise that epigenetic priming with AZA may represent an effective neoadjuvant therapeutic approach when complemented with CART therapy.


  1. To identify the optimal transmembrane and stalk CAR T-cell combination for sustained cytotoxity and proliferation advantage in organoid models of group3 medulloblastoma.
  2. To re-engineer the optimal CAR T-cell combination with next generation exhaustion-resistant mechanisms, with functional characterisation in co-culture organoid models of T-cells with group3 medulloblastoma.
  3. To analyse the enhanced efficacy of epigenetic modifiers in combination with the next generation CAR T-cells, using in vitro functional characterisation and methylation profiling.
  4. To evaluate the efficacy, persistancy and anti-tumour activity of the next generation CART plus epigenetic enhancer in vivo using multiple metastatic mouse models of group3 medulloblastoma.

6 - 12 month plan (eg experimental approaches, data collection, preliminary analyses):

To evaluate an array of therapeutic approaches in a high throughput setting, three-dimensional MB organoid cultures will be used to evaluate both T cell engineering and epigenetic drug approaches to enhance CAR-T persistence. This high-throughput system for CART screening is the latest advancement for cancer therapeutics, utilizing cell culture models which more closely mimic the in vivo micro-environment.


Year 1: Aim-1 and Aim-2

Year 2: Aim-2 and Aim-3

Year 3: Aim-4

Ethics Approval: REC 14/WM/1253


  1. Donovan, L. K. et al. Nat. Med. 26, 720-731 (2020).
  2. Vladoiu, M. C*., El-Hamamy, I*., Donovan, L. K*. et al. Nature 572, 67-73 (2019).
  3. Northcott, P. A. et al. Nature 547, 311–317 (2017).
  4. Brown, C. E. et al. Clin. Cancer Res. 21, 4062-72 (2015).
  5. Brown, C. E. et al. N. Engl. J. Med. 375, 2561-2569 (2016).