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Cytotherapy, 2013; 15: 632e640 REVIEW Biomarkers in T-cell therapy clinical trials SIMON F. LACEY MICHAEL KALOS Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA Abstract T-cell therapy represents an emerging and promising modality for the treatment of disease. Data from recent clinical trials of genetically modified T cells, most notably chimeric antigen receptor (CAR) T cells, have yielded dramatic clinical results and highlighted the potential for this approach to mediate anti-tumor activity. Continued progress in the development of such T-cell therapies will require the identification of the relevant biomarker strategies to support and guide clinical development of the candidate products. In this review, we review and discuss (i) principles for development and use of biomarkers in clinical research, (ii) the rationale and a strategy for the integration of biomarker data at all stages of the product development process, from preclinical studies through product manufacture and during the clinical trial and (iii) the different classes of biomarkers that are relevant to T-cell therapy trials. Throughout this review, we discuss how biomarkers can play a central role in the development of novel T-cell therapeutic agents and highlight how appropriately designed biomarker studies can provide critical insights to this process. Finally, we discuss future directions and challenges for the appropriate development of biomarkers to evaluate product bioactivity and treatment efficacy. Principles for development and use of clinical effects for any therapy is almost certainly not biomarkers in clinical research understood at the beginning of a clinical trial process, a fact that is particularly true when th