Tumour associated macrophages (TAMs) are implicated in cancer progression but can also exert anti-tumour activities. In this thesis, a strategy to redirect endogenous T cell cytotoxicity towards cancer supporting (M2-like) TAMs is explored. A panel of novel bi- and tri-valent T cell engagers (BiTEs/TriTEs) was generated, recognising CD3ε on T cells and M2-like macrophage markers CD206 or folate receptor β (FRβ). Primary human T cells activated by the BiTEs/TriTEs preferentially killed M2- over M1-polarised autologous macrophages, with EC50 values in the nanomolar range. This work represents the first to demonstrate the feasibility of redirecting T cells to kill macrophages. To avoid on-target off-tumour toxicities, we propose localising BiTE/TriTE expression to the tumour with an engineered oncolytic virus. We confirmed the feasibility of this approach by modifying an oncolytic adenovirus in early-phase clinical trials for solid cancers, enadenotucirev (EnAd), to express the BiTEs. Critically, T cell engager-armed EnAd retained its oncolytic and replicative capacities, whilst mediating BiTE expression from infected cancer cells. In immunosuppressive human malignant ascites samples, free and EnAd-encoded FRβ-targeting BiTEs (but not CD206-targeting T cell engagers) triggered endogenous T cell activation and IFN-γ production, leading to increased T cell numbers and a reduction in the number of CD11b+CD64+ ascites macrophages. Strikingly, surviving macrophages exhibited a general increase in M1-like marker expression, suggestive of a repolarisation of the microenvironment towards a more immune-responsive state. Taken together, this approach to deplete cancer-promoting TAMs in the context of the immune-stimulatory effects of BiTEs and oncolytic viruses offers a powerful new strategy for removing barriers to anti-tumour immunity in patients with cancer.