Antigen-Guided Synthetic Receptor Engineering for Safer T Cell Immunotherapy in Solid Tumors
Year: 2026
Type: review
Abstract: Engineered T cell therapies have transformed cancer immunotherapy, yet their application to solid tumors remains limited by Ag heterogeneity, shared Ag expression in normal tissues, immunosuppressive tumor microenvironments, and immune-mediated toxicities. These barriers indicate that improving cytotoxic potency alone is insufficient. Instead, therapeutic precision depends on how engineered T cells interpret antigenic and immunological context. We discuss solid tumor Ag biology as a determinant of receptor selection, therapeutic efficacy, and on-target off-tumor toxicity. We then examine chimeric Ag receptor, TCR-based, TCR-mimic, soluble TCR, T cell Ag couplers, TCR fusion constructs, and synthetic TCR and Ag receptor/HLA-independent TCR (STAR/HIT) systems with emphasis on Ag accessibility and signaling architecture. We further summarize toxicity mechanisms, including systemic inflammatory amplification, Ag distribution-dependent tissue injury, TCR cross-reactivity, and receptor-associated signaling dysregulation. Finally, we review programmable strategies, including logic-gated receptors, synthetic Notch circuits, quantitative Ag sensing, adaptor-controlled receptors, and genome editing, as approaches for spatial, temporal, and quantitative control. This Ag-guided framework provides a structured basis for matching Ag biology with receptor architecture and safety-control strategies, while emphasizing the need for careful translational evaluation in solid tumor T cell therapy.
Source: Immune Network
Institution: Dongduk Women's University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: Ministry of Food and Drug Safety
OpenAlex ID: W7224115245