Industrial production of therapeutic monoclonal antibodies is mostly performed in eukaryotic-based systems, allowing post-translational modifications mandatory for their functional activity. Nevertheless, the resulting elevated product cost limits therapy access to some patients, thus increasing medical inequality. To address this limitation, we conceptualized a novel immunotherapeutic approach aiming at redirecting a pre-existing polyclonal antibody response against Epstein-Barr virus (EBV) towards defined target cells. We engineered bi-modular fusion proteins (BMFPs), notably expressible in bacteria-based systems, comprising a Fc-deficient binding moiety (Nanobody, scFv) specifically targeting an antigen expressed at the surface of a target cell, fused to the P18 EBV antigen, which would recruit circulating endogenous anti-P18 IgG in individuals chronically infected by EBV. Opsonization of BMFP-coated target cells efficiently triggered antibody-mediated clearing effector mechanisms in vitro, such as the complement cascade, erythrophagocytosis by macrophages and FcγRIII-mediated activation of cellular pathways leading to antibody-dependent cell-mediated cytotoxicity (ADCC). When assessed in a mouse tumour model, therapy performed with an anti-huCD20 BMFP significantly led to increased mice survival and total cancer remission in some animals. These results indicate that BMFPs are versatile tools for redirecting an Epstein-Barr virus pre-existing immune antibody response towards pre-defined target cells and could represent potent and useful therapeutic molecules to treat a broad range of diseases.