T cell engagers: expanding horizons in oncology and beyond

Journal article : Review

Background/introduction: T cell engagers (TCEs) are engineered immunotherapeutic molecules designed to direct the body’s immune system against tumour or infected cells by bridging T cells and their targets, triggering potent cytotoxic responses. Over the past decade, TCE-based therapies have gained momentum in oncology, resulting in several FDA approvals for haematologic malignancies and showing growing promise in solid tumours. Objective: This review elaborates on TCE mechanisms of action, emphasising their ability to activate T cells, target tumour antigens, and modulate the tumour microenvironment. Methods/results: We also delve into the clinical outcomes demonstrating TCE efficacy, alongside challenges such as cytokine release syndrome, antigen heterogeneity, and short half-lives. Recent advances in TCE design have incorporated multispecific constructs and conditional activation strategies and expansion in target molecules has enabled broadening applications to non-oncology indications like autoimmune and infectious diseases. Moreover, the use of artificial intelligence (AI) has also accelerated TCE discovery by identifying favourable epitope interactions, reducing immunogenicity risks, and enhancing overall design efficiency. Conclusions: Looking further, these advances open up a new era to redefine success for TCEs in both cancer and beyond, offering hope for more effective, safer immunotherapies.

Authors: Albayrak, G; Wan, PK; Fisher, K; Seymour, LW

• Alternative title: Translational Therapeutics
• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: British Journal of Cancer
• Volume: 133
• Issue: 9
• Pages: 1241-1249
• Publication date: 2025-07-23
• Acceptance date: 2025-07-09
• DOI: 10.1038/s41416-025-03125-y
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Immunogenicity; Chimeric antigen receptor; Immunotherapy; Antigen; Medicine; Immune system; Cancer research; Immunology; Bioinformatics; Oncology; Biology
• Subtype: Review