The Landscape of Clinical Trials for TCR-T Cell Therapy.

Abstract

T cell receptor-engineered T cell (TCR-T) therapy represents an innovative tumor immunotherapy. Distinct from CAR-T, it recognizes MHC-restricted antigens to target tumor-specific antigens, exhibiting unique advantages for both solid and hematologic malignancies. To clarify the main trends, key targets, and therapeutic indications of TCR-T therapy, this study systematically summarizes the landscape of TCR-T-targeted clinical trials based on rigorous screening of the Trialtrove database, including 260 trials before April 1, 2026. Descriptive statistics were used to analyze the trials in terms of phase, status, distribution, disease indications, primary targets, and investigational drugs. Overall, TCR-T clinical research maintains sustained enthusiasm, dominated by early-phase trials (phase I and phase I/II, accounting for 88.85%), with active trials (open and planned) accounting for 51.92% and a considerable proportion of terminated trials (21.92%). Geographically, trials are concentrated in the United States and China, which serve as core collaboration nodes, with obvious geographical clustering characteristics in regional collaboration networks. In terms of disease indications, TCR-T therapy is more focused on solid tumors, with unspecified solid tumor, non-small cell lung cancer, and head/neck cancer as the top 3 indications. NY-ESO-1 is the most prominent target, followed by MAGE-A4, KRAS, PRAME, HPV16 E6/E7, and HBV surface antigen, with letetresgene autoleucel and LioCyx-M004 being the most investigated TCR-T products. Collectively, TCR-T therapy is a promising field in tumor immunotherapy with continuous research investment and advancing clinical progress.