Bispecific agents targeting tumor-cell surface antigens and activating receptors on T lymphocytes are being developed for solid tumors. Effective and safe strategies depend on target specificity and at least relative tumor-tissue confinement of T-cell activation. Novel evidence suggests that constructs targeting HER2 on tumor cells with the aim of providing costimulation (signal-2) to T lymphocytes via CD137 (4-1BB) are safe and can meaningfully invigorate antitumor responses in a proportion of patients.