期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-37883-y
关键词
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资金
- NHMRC of Australia [1100189]
- Pfizer Oncology
- Melbourne Research Scholarship (University of Melbourne) [58616]
- Cancer Therapeutics CRC (CTx) PhD Top Up Scholarship
- NHMRC Early Career Fellowship [1088703]
- National Breast Cancer Foundation (NBCF) Fellowship [PF-15-008]
- NHMRC New Investigator Grant [1140406]
- Priority-driven Collaborative Cancer Research Scheme [1120725]
- Cure Cancer Australia
- Peter MacCallum Cancer Centre Postgraduate Scholarship
- National Health and Medical Research Council of Australia [1088703, 1100189, 1140406] Funding Source: NHMRC
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 Braf(V600E)Cdkn2a(-/-)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 are sensitive to targeted inhibitors of BRAF(V600E) and MEK, responding in a manner consistent with human BRAF(V600E) melanoma. The YOVAL1.1 melanoma model is transplantable, immunogenic and sensitive to clinical therapies, making it a valuable platform to guide strategic development of combined targeted therapy and immunotherapy approaches in BRAF(V600E) melanoma.
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