Targeting T-Cell Costimulation to the Surface of Tumor Cells.

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 cluster of differentiation 137 (4-1BB) are safe and can meaningfully invigorate antitumor responses in a proportion of patients. See related article by Piha-Paul et al., p. 288.