Bispecific and multispecific T-cell engagers: advancing the future of immunotherapy

T-cell engagers (TCEs) represent an emerging class of immunotherapies that harness T cells' cytotoxic power to eliminate diseased cells-a transformative future therapeutic strategy. TCEs form immunological synapses to trigger potent immune responses, with proven efficacy in blood cancers; research expands their use to solid tumors via innovative molecular design and improved safety profiles. Beyond oncology, TCEs hold promise in autoimmune disorders by eliminating autoreactive cells, offering novel avenues for diseases like lupus. However, achieving optimal outcomes without disrupting immune homeostasis remains a challenge. Key obstacles-on-target off-tumor toxicity, cytokine release syndrome, tumor antigen loss, and T cell exhaustion-limit broader adoption. Current research addresses these via enhanced specificity, optimized design, improved druggability, and synergistic combinations. This review analyzes TCEs' mechanisms, challenges, innovations and applications, highlights our pipeline advances, and advocates sustained innovation to broaden TCE use across diseases.