Harnessing pre-clinical lung cancer patient models for precision immuno-oncology (360G-Wellcome-209199_Z_17_Z)
<p>Only 16% of non-small cell lung cancer (NSCLC) patients survive for 5 years. Improvement in survival has been slow as the histological and genomic features of the disease are heterogeneous. Tumour heterogeneity poses a challenge for therapy development and suggests the importance of a personalised medicine approach. One approach is to expand the subset of tumour-infiltrating lymphocytes (TILs) that target neoantigens generated by tumour mutations; however, the lack of model systems that recapitulate the complexity of human disease is a significant barrier to research in this area. Patient-derived xenografts (PDXs) have considerable advantages over murine cancer models and cell lines so I will generate PDX models from patients enrolled in the TRACERx clinical study, which aims to delineate the evolutionary trajectories of NSCLC through multi-region genetic analyses of primary, recurrence and metastatic tumours. My first goal is to establish the extent to which PDX tumours represent patient intratumour heterogeneity using the extensive TRACERx dataset. I will further use these models - along with patient-matched TILs - in <em>in vitro</em> and <em>in vivo</em> assays to investigate the key determinants of the ability of TILs to destroy cancer cells and to investigate the effect of dual checkpoint inhibitor and TIL therapy.</p>
£250,000 08 Nov 2017
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Amount Awarded | 250000 |
Applicant Surname | Hynds |
Approval Committee | Basic Science Interview Committee |
Award Date | 2017-11-08T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Sir Henry Wellcome Postdoctoral Fellowship |
Internal ID | 209199/Z/17/Z |
Lead Applicant | Dr Robert Hynds |
Planned Dates: End Date | 2022-01-02T00:00:00+00:00 |
Planned Dates: Start Date | 2018-01-02T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Charles Swanton |