In cancer immunotherapy, lymphocytes can be modified to express T cell receptors (TCRs) specific for particular tumour antigens. However, these antigens are mostly self-antigens, and T cells that bind strongly to self-antigens are eliminated to avoid autoimmune responses. Obenaus et al. have developed a new strategy for generating T cells that can recognize tumours as exogenous antigens. They generated transgenic mice with T cells expressing a repertoire of human TCRs instead of mouse TCRs. They then inoculated human cancer antigens into these mice, inducing a reactive T cell response. The authors isolated the TCRs specific for certain tumour antigens and observed an antitumour effect in vivo in a different animal model. The DNA encoding the resulting high-affinity TCRs could then be transferred into human T cells for adoptive therapy.