PhD CAR T Therapy for Improved Survival of Children Diagnosed with DIPG

Join the Cancer Signalling Research Group as they investigate immunotherapy approaches against the fatal paediatric brain cancer ‘diffuse intrinsic pontine glioma’. Use cell and molecular biochemistry, quantitative mass spectrometry and animal models to evaluate a novel anti-DIPG CAR-T therapy.

Diffuse intrinsic pontine glioma (DIPG) are a type of diffuse midline glioma (DMG) primarily diagnosed in children. With no therapies available (except palliateive radiation therapy), median survival is 9-11 months. DMG/DIPG are considered an “immunologically cold” tumour, meaning there are very few immune cells interacting with, or situated within, the area of the malignancy. For many other (non-cold) cancers, the patient’s immune system can recognise tumour cells as ‘bad’, leading to activation of the immune cells and the body launching a fight against the cancerous cells. In the case of melanoma and some blood cancers, immune-based therapies have vastly improved patient survival; the treatment trains the body to recognise and fight tumour cells.

Thanks to our recent and ongoing work funded by the Little Legs Foundation we have identified a protein marker on the surface of DMG cells that we believe can be exploited in the design of a DMG-specific CAR T immunotherapy. In the field of immuno-oncology, it is important to select a target that is tumour-specific, so that the immune system (in this case the T cells) are trained only to find and fight cancer cells, rather than indiscriminately combatting both tumour and healthy tissue.

Our potential CAR T target is a cell-surface protein that we have found to be abundant on the outside of DMG cells, but is scarcely so on healthy brain cell controls. Buoyed by our discovery, we searched the scientific literature to understand what is known of this protein, and found it reported to be upregulated in the most common and aggressive adult brain cancer (glioblastoma), as well as in low-grade glioma. Our protein of interest has also been shown to be associated with more aggressive disease (vs cancers that do not express, or express a lower level of the protein).

With this in mind, we must ask the question – could a CAR T therapy targeting our protein of interest provide a long overdue survival benefit for DMG patients and their families?? To assess this, the candidate will: – Confirm the protein of interest has very limited expression on healthy tissues – if not, the CAR T would indiscriminately find and launch an immune attack on both tumour and healthy cells, leading to detrimental side effects.

To do so, the candidate will develop a tissue microarray or ‘TMA’ (a collection of different healthy tissues alongside DMG samples) to comprehensively evaluate the target. – Develop an antibody targeting the protein of interest – with tumour-specific expression confirmed via TMA, we will develop an antibody that recognises our protein. The selectivity of the antibody to DMG vs healthy tissue will be evaluated using the above-mentioned TMA, and with selectivity/specificity confirmed, its safety and on/off-target effects evaluated in mouse-modelled DMG.

Thanks to links with an industry collaborator, a CART T will be manufactured using the uniquely designed antibody, which the candidate will once again test for specificity, safety and effectiveness. This will involve cell-based and animal-based models and produce a vital dataset required if we are to progress the approach to clinical trial.

PhD Scholarship details

Funding: $28,854 per annum (2022 rate) indexed annually. For a PhD candidate, the living allowance scholarship is for 3.5 years and the tuition fee scholarship is for four years. For an MPhil candidate, the living allowance and tuition fee scholarships are two years. Scholarships also include up to $1,500 relocation allowance and Overseas Student Health Cover at single rate, for an international candidate.

Supervisor: Associate Professor Matt Dun

Available to: Domestic and International students

Either PhD or MPhil

Eligibility Criteria

An undergraduate degree in Science, Medical Science, Biotechnology or related field.

The applicant will need to meet the minimum eligibility criteria  for admission.

Application Procedure

Please ensure that you review the Little Legs Foundation Scholarship Conditions prior to preparing your application for this scholarship.

Interested applicants should send an email expressing their interests including a statement on how you think we can harness the power of the immune system to improve the treatment of paediatric brain cancer. Also include detail of both professional and research achievements in your CV and scanned copies of academic transcripts.

Any applicant that does not submit the required documentation above by the application closing date will not be considered for selection.

Please send the email expressing interest to Alicia.Douglas@newcastle.edu.au by 5pm on 09 December 2022.