Poster Presentation Australasian Melanoma Conference 2018

A novel immunogenic mouse model of melanoma for the preclinical assessment of combination targeted and immune-based therapy (#114)

Emily Lelliott 1 2 3 , Carleen Cullinane 1 2 4 , Claire A Martin 1 , Rachael Walker 1 , Kelly M Ramsbottom 1 , Fernando Guimaraes 3 5 , Shatha Abuhammad 1 , Richard J Young 1 , Laura Kirby 1 , Alison Slater 1 , Peter Lau 1 2 , Katrina Meeth 6 , Jane Oliaro 1 2 , Nicole Haynes 1 2 6 , Grant A McArthur 1 2 7 , Karen E Sheppard 1 2 8
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, VIC, Australia
  3. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
  4. Department of Pathology, University of Melbourne, Melbourne, VIC 3000, VIC, Australia
  5. Division of Molecular Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  6. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
  7. Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia
  8. Department of biochemistry and molecular biology, University of Melbourne, Melbourne, VIC 3000, VIC, Australia

Both targeted therapy and immunotherapy have been used successfully to treat melanoma, but the development of resistance and poor response rates to the individual therapies has limited their success. Designing rational combinations of targeted therapy and immunotherapy may overcome these obstacles, but requires assessment in preclinical models with the capacity to respond to both therapeutic classes. Herein, we describe the development and characterization of a novel, immunogenic variant of the BrafV600ECdkn2a-/-Pten-/- YUMM1.1 tumor model that expresses the immunogen, ovalbumin (YOVAL1.1). We demonstrate that, unlike parental tumors, YOVAL1.1 tumors are immunogenic in vivo and can be controlled by immunotherapy. Importantly, YOVAL1.1 tumors retained sensitivity to BRAFV600E- and MEK-targeted therapy, responding in a manner consistent with human BRAFV600E melanoma. The YOVAL1.1 melanoma model is transplantable, immunogenic and sensitive to clinical therapies, making it a cost-effective platform to guide strategic development of combined targeted- and immune-therapy approaches in BRAFV600E melanoma.