Advances in the treatment of metastatic melanoma include the recent approval of the immunotherapy ipilimumab, an anti-CTLA-4 monoclonal antibody, and of the targeted therapies vemurafenib, dabrafenib and trametinib, which are mitogen-activated protein kinase (MAPK)-pathway inhibitors. Cancer immunotherapy also includes adoptive transfer of autologous tumour-specific chimeric antigen receptor (CAR) T cells. CAR T cells are responsible for significant tumour responses in leukaemia and neuroblastoma patients, and we have manufactured GD2-specific CAR T cells to be used in patients with advanced GD2+ melanoma. However, although these promising new targeted- and immuno-therapies can produce complete or partial tumour responses, tumour resistance via alteration or bypass of the targeted molecules inevitably occurs. This has been widely reported for the BRAF inhibitors dabrafenib and vemurafenib, and has also occurred in CAR T cells specific for CD19+leukaemia. Combination therapies have been proposed as a way to exploit the high-level but short-term responses associated with kinase-inhibitor therapies and the low-level but longer-term responses associated with immunotherapy, and could potentially overcome tumour resistance by targeting multiple tumour-associated molecules. To this end, we have investigated the effects of vemurafenib, dabrafenib and trametinib on the function of our GD2-CAR T cells and found that only vemurafenib inhibited effector functions at concentrations equivalent to reported plasma concentrations in treated patients. We have also found that GD2-CAR T cells can kill BRAFi-resistant, CTL cross-resistant melanoma cell lines, and are uninhibited by PD1/PDL1 interactions, indicating that GD2-CAR T cells are a strong candidate for use in combination with dabrafenib-targeted therapy. This hypothesis will be tested in our imminent CARPETS Phase I clinical trial of autologous GD2-CAR T cells in patients with advanced GD2+ melanoma and solid tumours.