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


Lelliott, EJ; Cullinane, C; Martin, CA; Walker, R; Ramsbottom, KM; Souza-Fonseca-Guimaraes, F; Abuhammad, S; Michie, J; Kirby, L; Young, RJ; SLATER, A; Lau, P; Meeth, K; Oliaro, J; Haynes, N; McArthur, GA; Sheppard, KE
2019-02-04
Scientific Reports
Journal Article
9
1
1225
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.
Springer Nature
Immunology
10.1038/s41598-018-37883-y
30718660
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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Creation Date 2019-03-13 08:04:17 Last Modified 2019-03-13 09:12:47