Immunologic effects of an orally available BRAFV600E inhibitor in BRAF wild-type murine models.
Vemurafenib is an orally available small molecule that targets constitutively activated BRAFV600E, an integral part of the MAPK pathway involved in melanomagenesis. We examined the effects of vemurafenib on cytokine production and antitumor response in a BRAF wild-type (WT) non-tumor-bearing murine model and a BRAF WT murine insulinoma system to determine its effect on immune function during immunotherapy. We demonstrate no significant effect from vemurafenib on CD4+ and CD8+ T-cell cytokine production or on a T-cell-mediated antitumor response. Our data demonstrate that vemurafenib does not significantly affect BRAF WT targets, suggesting that there may be a role for combining vemurafenib treatment with T-cell-directed immunotherapy.
Division of Hematology/Oncology, Scripps Clinic and Green Hospital, La Jolla, CA, USA.
Gregory S
GS
Vosganian
Rinke
R
Bos
Linda A
LA
Sherman
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D016219:Immunotherapy, Adoptive; D007211:Indoles / Q000494:pharmacology*; D007340:Insulinoma / Q000188:drug therapy*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000077484:Vemurafenib
D007211:Indoles; D007376:Interleukin-2; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000077484:Vemurafenib; D007371:Interferon-gamma; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf