Article Text

Download PDFPDF

EPV003/#326 An integrated genomic, proteomic and immunopeptidomic approach to discover novel tumour neoantigens in an immunologically cold ovarian cancer for personalised T-cell receptor therapy
  1. GY Ho1,2,
  2. P Faridi3,
  3. J Wu1,
  4. H Barker4,5,
  5. T Nguyen-Dumont1,6,
  6. J Chang1,
  7. A Fell1,
  8. P Eggenhuizen1,
  9. J Steen1,
  10. T Manolitsas2,
  11. S Frentzas1,2,
  12. J Bedo4,7,
  13. C Vandenberg4,5,
  14. T Papenfuss4,5,
  15. C Scott4,5,
  16. J Ooi1 and
  17. E Segelov1,2
  1. 1Monash University, School of Clinical Sciences, Clayton, Australia
  2. 2Monash Health, Oncology Department, Clayton, Australia
  3. 3Monash University, Monash Biomedicine Discovery Institute, Clayton, Australia
  4. 4Walter and Eliza Hall Institute of Medical Research, Cancer Biology and Stem Cells Division, Parkville, Australia
  5. 5University of Melbourne, Department of Medical Biology, Parkville, Australia
  6. 6University of Melbourne, 6. Departcomputing and Information Systems, Parkville, Australia
  7. 7University of Melbourne, Department of Computing and Information Systems, Parkville, Australia


Objectives Ovarian carcinosarcoma (OCS) are rare aggressive cancers with poor prognosis and limited effective treatments. The tumour mutation burden in OCS is often low. Therefore, these tumours are immunologically ‘cold’ and relatively irresponsive to single agent immunotherapy. We explored tumour neoantigen discovery in an OCS using various genomic and proteomic platforms for personalised T-cell receptor (TCR) therapy.

Methods Whole genome sequencing (WGS) was performed on SFRC01177 OCS tumour specimen taken at surgery. Fresh tumour specimens obtained at surgery and biopsy at recurrence were engrafted subcutaneously in NOD-scidIL2Rgammanull (NSG) to generate a paired patient derived xenograft (PDX) model. Whole exome sequencing and RNA sequencing (WES/RNAseq) together with nano-ultra-performance liquid chromatography coupled to high-resolution mass spectrometry were performed on the snap frozen tumours from the baseline and recurrent PDX for tumour neoantigen (TNA) discovery.

Results A total of 6,500 mutant TNA were predicted in silico from the baseline WGS data which were narrowed down to 65 and 33 respectively based on the baseline and recurrent PDX tumours WES/RNAseq data. The immunopeptidomic analysis revealed over 100 major histocompatibility complex bound antigens including mutant, spliced and cancer testis antigens. The PDX was re-established in NSG MHCnull mouse model and was shown to retain the platinum refractory in vivo response as well as to tolerate 1 million HLA-matched donor CD8+ T-cell injections.

Conclusions We have discovered multiple tumour specific neoantigens using the comprehensive TNA discovery platforms, which will direct our TCR engineering. In parallel, we have also established an OCS PDX model suitable for cell-based therapy testing.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.