Abramson Cancer Center and the Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-5156, USA.
Immunity. 2013 Jul 25;39(1):49-60. doi: 10.1016/j.immuni.2013.07.002.
Adoptive T cell transfer for cancer and chronic infection is an emerging field that shows promise in recent trials. Synthetic-biology-based engineering of T lymphocytes to express high-affinity antigen receptors can overcome immune tolerance, which has been a major limitation of immunotherapy-based strategies. Advances in cell engineering and culture approaches to enable efficient gene transfer and ex vivo cell expansion have facilitated broader evaluation of this technology, moving adoptive transfer from a "boutique" application to the cusp of a mainstream technology. The major challenge currently facing the field is to increase the specificity of engineered T cells for tumors, because targeting shared antigens has the potential to lead to on-target off-tumor toxicities, as observed in recent trials. As the field of adoptive transfer technology matures, the major engineering challenge is the development of automated cell culture systems, so that the approach can extend beyond specialized academic centers and become widely available.
过继性 T 细胞转移治疗癌症和慢性感染是一个新兴领域，最近的试验显示出了前景。基于合成生物学的 T 淋巴细胞工程改造，使其表达高亲和力的抗原受体，可以克服免疫耐受，这一直是免疫治疗策略的主要限制。细胞工程和培养方法的进步，使高效的基因转移和体外细胞扩增成为可能，从而更广泛地评估了这项技术，使过继性转移从一种“精品”应用发展到主流技术的前沿。该领域目前面临的主要挑战是提高工程化 T 细胞对肿瘤的特异性，因为靶向共享抗原有可能导致靶标外的肿瘤毒性，这在最近的试验中已经观察到。随着过继转移技术领域的成熟，主要的工程挑战是开发自动化细胞培养系统，以便该方法不仅可以在专门的学术中心使用，而且可以广泛应用。
