Host immunity contributes to the antimelanoma activity of BRAF inhibitors

DA Knight; SF Ngiow; M Li; T Parmenter; S Mok; A Cass; NM Haynes; K Kinross; H Yagita; RC Koya; TG Graeber; A Ribas; GA McArthur; MJ Smyth

Journal article

Host immunity contributes to the antimelanoma activity of BRAF inhibitors

DA Knight, SF Ngiow, M Li, T Parmenter, S Mok, A Cass, NM Haynes, K Kinross, H Yagita, RC Koya, TG Graeber, A Ribas, GA McArthur, MJ Smyth

Journal of Clinical Investigation | Published : 2013

DOI: 10.1172/JCI66236

Abstract

The BRAF mutant, BRAFV600E, is expressed in nearly half of melanomas, and oral BRAF inhibitors induce substantial tumor regression in patients with BRAFV600E metastatic melanoma. The inhibitors are believed to work primarily by inhibiting BRAFV600E-induced oncogenic MAPK signaling; however, some patients treated with BRAF inhibitors exhibit increased tumor immune infiltration, suggesting that a combination of BRAF inhibitors and immunotherapy may be beneficial. We used two relatively resistant variants of BrafV600E-driven mouse melanoma (SM1 and SM1WT1) and melanoma-prone mice to determine the role of host immunity in type I BRAF inhibitor PLX4720 antitumor activity. We found that PLX4720 tr..

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University of Melbourne Researchers

Grant McArthur Author

Related Projects (3)

2007 PROGRAM GRANT - (IMMUNE REGULATION, EFFECTOR FUNCTION AND HUMAN IMMUNOTHERAPY)

The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progress..

2007 PROGRAM GRANT - (IMMUNE REGULATION, EFFECTOR FUNCTION AND HUMAN IMMUNOTHERAPY)

The immune system plays an important role in protecting the host from viral and bacterial infections, and inhibits cancer onset and progress..

Understanding Inhibition of BRAF in Melanoma

Recent clinical studies have shown that the most common mutation found in melanoma in the gene BRAF can be successfully targeted for treatme..

Grants

Awarded by Japan Society for the Promotion of Science

Funding Acknowledgements

[ "Grant A. McArthur declares financial research support from Pfizer and Millenium.", "We thank Qerime Mundrea for her care and maintenance of the mouse colonies. The vemurafenib analog PLX4720 was provided by Gideon Bollag from Plexxikon Inc. This work was supported by the National Health and Medical Research Council of Australia (NHMRC) program grant (454569) and project grant (1002655) and the Victorian Cancer Agency. M.J. Smyth received support from a NHMRC Australia Fellowship. S.F. Ngiow was supported by a Cancer Research Institute PhD scholarship. G.A. McArthur received support from a NHMRC Practitioner Fellowship." ]