Revolutionizing cancer immunotherapy: T cell engagers beyond hematologic malignancies toward solid tumors

T cell engagers (TCEs) are a class of T cell-redirecting therapeutics that enhance antitumor immunity by bringing T cells into close proximity with malignant cells. Following their success in hematologic malignancies, TCEs are now being increasingly investigated for the treatment of solid tumors. The recent approval of tarlatamab for small cell lung cancer (SCLC) offers renewed hope in this setting. Nevertheless, clinical efficacy in solid tumors remains limited by immunosuppressive tumor microenvironments (TME), on-target/off-tumor toxicity, and intrinsic or acquired resistance to TCEs. This review summarizes recent advances in TCE development for solid tumors, including refinements in molecular design, biomarker-guided patient selection, and rational combination strategies aimed at overcoming resistance and improving therapeutic outcomes. We also discuss emerging next-generation approaches, such as engager platforms that redirect other immune effector cells. Collectively, these innovations underscore the potential of more precise and effective engager-based therapies for solid tumors.