工程化免疫效应细胞生物标志物检测的专家组综述与实践指南

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape across several hematologic malignancies.

However, variability in biomarker assays, timing, and interpretation across clinical centers hampers the comparability of results, limits translational insight, and constrains evidence-based decision-making. As immune effector cells expand into emergent platforms and new indications, standardized biomarker frameworks are increasingly critical for optimizing patient outcomes and prospectively advancing the field. These expert panel recommendations, developed by the American Society for Transplantation and Cellular Therapy Committee on Cellular Therapy, aim to harmonize biomarker testing practices in CAR T-cell therapy. It provides evidence-based recommendations on the selection, timing, and clinical application of laboratory-based, cytokine, and CAR T-cell monitoring assays to inform toxicity management, guide treatment decisions, and support future research. A multidisciplinary expert panel reviewed current literature, clinical practices, and available evidence on biomarker use in CAR T-cell recipients. Through iterative consensus, the group established recommendations for routine laboratory assessments, cytokine profiling, and CAR T-cell pharmacokinetic monitoring. Biomarkers were stratified by clinical utility into "must-have," "can-have," and "nice-to-have" tiers based on clinical relevance, reproducibility, intent, and biological significance.

The panel recommends comprehensive baseline laboratory testing-including metabolic panels, complete blood counts, inflammatory markers, and disease-specific biomarkers-prior to lymphodepletion. Serial measurements of inflammatory markers and targeted cytokines (eg, interleukin (IL)-6, interferon gamma, tumor necrosis factor alpha, chemokine C-X-C motif 9 (CXCL9)) are advised during acute toxicity phases. CAR T-cell monitoring by flow cytometry or ddPCR should occur at defined intervals to assess expansion, persistence, and therapeutic response. Both cytokines and CAR-T kinetics carry great promise as potential dynamic predictors of toxicity or nonresponse.

Harmonized timing, fold-change calculations, and standardized reporting are critical for enabling cross-study comparability and advancing biomarker-driven care. Standardized biomarker testing is essential to improve patient outcomes, enable precision toxicity management, and accelerates CAR T-cell therapy innovation.

These American Society for Transplantation and Cellular Therapy consensus recommendations provide a practical framework for clinical implementation and future research, bridging routine practice with next-generation biomarker-driven strategies.