The past decade has seen the emergence of a novel form of adoptive cellular therapy in patients involving the genetic modification of cytotoxic T lymphocytes (CTLs) to express chimeric antigen receptors (CARs). Although CAR-T cell therapy has recently shown some striking results in patients with haematological cancers, the success against solid cancers has been more modest. The major challenges for current CAR T cell therapy include maintaining efficacy in the hostile tumour microenvironment and effectively targeting a high frequency of CAR T cells to the tumour. We hypothesized that a vaccine composed of a recombinant poxvirus could be used as an antigen delivery vehicle to specifically activate CAR T cells through their T cell receptors (TCRs) and change the tumour microenvironment, allowing the recruitment and activation of CAR T cells. In this project, we crossed CAR transgenic mice with pMEL-1 mice. T cells from these mice have dual specificity – a CAR reactive against Her2 tumour antigen and TCR reactive against the melanoma antigen gp100 (CARaMEL). Adoptive transfer of CARaMEL T cells, followed by TCR-specific stimulation by systemic administration of vaccinia-gp100 resulted in robust destruction of large established breast tumours in mice. The mice cleared of tumour remained tumour-free for over 100 days. Treatment was associated with off-tumour effects against a proportion of normal melanocytes, leading to patchy vitiligo. Tumour regression was associated with enhanced infiltration of CARaMEL T cells in tumour tissue. Taken together, our study has shown for the first time that the stimulation of CAR T cells through their endogenous TCR using a poxvirus resulted in enhanced T cell infiltration to tumour sites and destruction of large established tumour in mice. In addition, our data provide valuable information for the development of CAR T cell therapies for patients with solid cancers.