BRAF(V600) Inhibitor GSK2118436 Targeted Inhibition of Mutant BRAF in Cancer Patients Does Not Impair Overall Immune Competency

The V600 mutant BRAF inhibitor treatment does not affect the number of CD4⁺/CD8⁺ T, B, or NK cells in the blood of patients treated. PBMCs of 13 patients with tumors bearing the V600E BRAF mutation were treated with the GSK2118436 V600 mutant BRAF inhibitor for 2 cycles (4 weeks for each cycle). PBMCs before treatment (baseline) and after cycles 1 and 2 were stained with CD3-AmCyan, CD19-FITC, CD8-APC, CD56-PE-Cy7, and CD4-APC-Cy7. The number of CD8⁺ T cells (A), CD4⁺ T cells (B), B cells (C), or NK cells (D) per microliter of blood did not change throughout the course of treatment. The frequency of these cell types also stayed constant throughout the treatment (Supplementary Fig. S2).

The V600 mutant BRAF inhibitor treatment does not affect CD4⁺ and CD8⁺ memory T-cell responses to recall antigens. GSK2118436 V600 mutant BRAF inhibitor-treated patients were tested in vitro before treatment (baseline) and after cycles 1 and 2 in an IFN-γ ELISPOT assay in the presence of a CEF (CMV/EBV/Flu) peptide library containing 43 peptides, chemically inactivated TT, a positive (PMA/ionomycin), or negative controls (no peptide; A). CD8⁺ T-cell memory responses against CEF peptides (B) and CD4⁺ T-cell memory responses against a chemically inactivated TT protein (C) were measured and represented as fold change from baseline.