Biomarker-empowered precision navigation of CAR-T cell therapy.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies and continues to advance clinically. However, its broader application is hindered by heterogeneous efficacy, limited response durability, antigen-negative relapse, and both acute and delayed toxicities. Biomarkers are therefore critical for predicting clinical outcomes, optimizing product design, refining patient selection, evaluating early responses, and monitoring toxicities. In this review, we summarize current biomarkers across key biological compartments that determine CAR-T efficacy and safety: host-derived factors including baseline inflammatory profiles, immune composition, and T-cell fitness; product-related features such as CAR structure, cellular subsets, metabolic state, expansion, and persistence; tumor-derived markers including antigen expression, genomic characteristics, minimal residual disease, circulating tumor DNA, and tumor microenvironment. We also outline biomarkers associated with major CAR-T-related toxicities. Finally, we discuss how high-parameter flow cytometry, single-cell multi-omics, extracellular vesicles, and novel CAR platforms are advancing biomarker development. Collectively, these findings support a shift from individual candidate markers toward integrated longitudinal frameworks to guide precision CAR-T therapy and further improve efficacy, durability, and safety.