Project: Towards Engineered T Cells for Osteosarcoma

Project: Towards engineered T cells for osteosarcoma

• Primary supervisor: Dr Martin Pule
• Secondary surpervisor: Dr Karin Straathof

This is a 4-year studentship funded by the Bone Cancer Trust, which covers tuition fees at the UK rate and a stipend of £18,065 per year. The earliest start date for this studentship is October 2022.

Closing date: 12^th September 2022, 17.00 (BST)

Description

Aim of this project is develop engineered T cells for osteosarcoma. Osteosarcoma is the most common bone cancer in adolescents and young adults (80% of the patients are younger than 25 years old) but nevertheless are rare cancer. Intensification of chemotherapy at diagnosis or relapse has not modified patient outcome and survival of patients with osteosarcoma has not improved in the last four decades.

Here we aim to develop chimeric antigen receptors (CAR) T cells for osteosarcoma. CARs graft the specificity of an antibody onto a T cell. CAR T cell therapy has an established role in the treatment of refractory B cell malignancies. In this setting, CD19 CAR T cell therapy can result in durable remissions in chemo-refractory patients. There is now considerable interest in applying CAR T cell therapy to solid cancers but lack of convenient tumour targets (such as CD19), hostile immune microenvironment and tumour heterogeneity makes application more difficult than in lymphoid malignancies.

Disialoganglioside (GD2) is ex-pressed at high density in certain cancers including osteosarcoma and neuroblastoma while only expressed at low level in peripheral pain fibres and brain parenchyma. We have developed a GD2 CAR which can discriminate high level pathological expression from low level physiological ex-pression. We have tested this CAR in children with relapsed / refractory neuroblastoma (https://pubmed.ncbi.nlm.nih.gov/33239386/). We observed robust, but transient anti-tumour activity. This work demonstrates that GD2 can be safely targeted. Now we need to further engineer the CAR T cells to resist and modulate the hostile tumour microenvironment to convert transient into sustained anti-tumour activity. 

For more information, please download the job specification below.

Application Procedure

For more information and to apply, please download the following documents:

• Job Specification

  Job Specification
   

• Equal Opportunities form

  Equal Opportunities form

Shortlisting and notification will likely take place W/C 19th September. Queries about the application procedure or recruitment process should be directed to: ci.scholarships@ucl.ac.uk