Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-4283, USA.
Cytotherapy. 2013 Jun;15(6):632-40. doi: 10.1016/j.jcyt.2013.01.002. Epub 2013 Feb 14.
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.
T 细胞疗法代表了一种新兴且有前途的疾病治疗模式。最近的基因修饰 T 细胞临床试验数据，尤其是嵌合抗原受体 (CAR) T 细胞，取得了显著的临床效果，并凸显了这种方法介导抗肿瘤活性的潜力。为了继续推进此类 T 细胞疗法的发展，需要确定相关的生物标志物策略，以支持和指导候选产品的临床开发。在这篇综述中，我们回顾和讨论了：（i）在临床研究中开发和使用生物标志物的原则；（ii）在产品开发过程的所有阶段（从临床前研究到产品制造以及临床试验期间）整合生物标志物数据的基本原理和策略；（iii）与 T 细胞治疗试验相关的不同类别的生物标志物。在整篇综述中，我们讨论了生物标志物如何在新型 T 细胞治疗药物的开发中发挥核心作用，并强调了如何通过适当设计的生物标志物研究为这一过程提供关键见解。最后，我们讨论了未来适当开发生物标志物以评估产品生物活性和治疗效果的方向和挑战。
