The novel immunotherapy naptumomab estafenatox, an anti-5T4 antibody fused with a staphyloccocal superantigen is under investigation as a treatment for a variety of different tumour types. However, the final analyses of a phase II/III clinical trial comparing the efficacy of naptumomab estafenatox administered with interferon (IFN)-α versus IFN-α monotherapy reveal no significant diiference in overall survival between patients who received naptumomab estafenatox plus IFN-α versus those who received IFN-α alone. Despite the failure to achieve any differences in overall survival, this approach might be effective in certain biomarker-defined patient subgroups.