Synthetic Biology Group, Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, USA.
Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Rev Cancer. 2019 Apr;19(4):187-195. doi: 10.1038/s41568-019-0121-0.
Engineered immune-cell-based cancer therapies have demonstrated robust efficacy in B cell malignancies, but challenges such as the lack of ideal targetable tumour antigens, tumour-mediated immunosuppression and severe toxicity still hinder their therapeutic efficacy and broad applicability. Synthetic biology can be used to overcome these challenges and create more robust, effective adaptive therapies that enable the specific targeting of cancer cells while sparing healthy cells. In this Progress article, we review recently developed gene circuit therapies for cancer using immune cells, nucleic acids and bacteria as chassis. We conclude by discussing outstanding challenges and future directions for realizing these gene circuit therapies in the clinic.
基于工程化免疫细胞的癌症疗法在 B 细胞恶性肿瘤中显示出了强大的疗效，但仍存在一些挑战，如缺乏理想的可靶向肿瘤抗原、肿瘤介导的免疫抑制以及严重的毒性等，这些因素限制了它们的治疗效果和广泛适用性。合成生物学可以用来克服这些挑战，创造更强大、有效的适应性疗法，使这些疗法能够特异性地靶向癌细胞，同时保护健康细胞。在这篇进展文章中，我们综述了最近利用免疫细胞、核酸和细菌作为底盘开发的用于癌症的基因回路疗法。最后，我们讨论了在临床上实现这些基因回路疗法所面临的突出挑战和未来方向。
