In recent years, chimeric antigen receptor (CAR) T-cell therapy has become a promising treatment for cancer therapy. Despite this progress, a significant proportion of patients experience resistance to CAR-T therapy. Cancer cells may be insensitive to destruction by CAR-T cells, known as intrinsic resistance. This resistance is responsible for a very significant proportion of CAR-T therapy failure in all tumour types and is an additional challenge to the efficacy of CAR-T cells in the treatment of solid tumours. Many of the intrinsic resistance mechanisms are regulated at the epigenetic level. Recently, several epigenetic inhibitors have been developed and tested in cancer. So far, the main focus of most studies has been the direct cytotoxic effect, and few studies have investigated the ability to reverse the resistant phenotype of cancer cells to CAR-T therapy. There is a need for a systematic approach to identify new drugs that sensitise the tumour cell to destruction by CAR-T cells. By expressing flaying luciferase (fLuc) in murine solid tumour lines expressing the EGFRvIII target antigen, we have established a simple, accurate, sensitive and robust protocol to detect epigenetic sensitisers. We demonstrate the efficacy of our protocol and identify several epigenetic inhibitors capable of sensitising tumour cells to killing by an anti-EGFRvIII CAR. Furthermore, we show that these inhibitors achieve sensitisation at doses lower than those required to induce toxicity. Further research into the mechanisms behind epigenetic sensitisation is required. Our study supports the use of epigenetic inhibitors as sensitising agents for CAR-T cell therapy.