Oral Presentation Melbourne Immunotherapy Network Winter Retreat 2018

A novel preclinical platform for evaluating targeted therapy and immunotherapy combinations in BRAFV600E melanoma (#45)

Emily J Lelliott 1 2 3 , Carleen Cullinane 1 2 4 , Claire A Martin 2 , Rachael Walker 2 , Kelly Ramsbottom 2 , Fernando Guimaraes 3 5 , Shatha Abuhammad 2 , Laura Kirby 2 , Richard Young 2 , Peter Lau 1 2 , Katrina Meeth 6 , Jane Oliaro 1 2 , Nicole Haynes 1 2 4 , Grant McArthur 1 2 7 , Karen Sheppard 1 2 8
  1. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, VIC, Australia
  2. Peter MacCallum Cancer Centre, Melbourne, 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, in contrast to the commonly used mouse melanoma model B16, YOVAL1.1 tumors are sensitive 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.