Hwang William Y K, Muzammil Ezzah Mohamed
Regenerative Medicine Institute of Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore; Department of Haematology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore.
Regenerative Medicine Institute of Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore; Department of Haematology, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore.
Cytotherapy. 2025 Feb 11. doi: 10.1016/j.jcyt.2025.01.017.
2024 marked a transformative phase for cell and gene therapy (CGT) with significant advancements in scientific innovation, regulatory approvals and commercialization milestones. This review highlights key developments in CGT, including innovations in chimeric antigen receptor (CAR)-T therapies, mesenchymal stromal cells (MSCs), gene editing and regenerative medicine, alongside challenges in scalability, regulation and safety. Prominent breakthroughs in CAR-T technology extended its applications beyond oncology to autoimmune diseases, including lupus and systemic sclerosis. Gene therapies achieved major milestones, exemplified by regulatory approval for the treatment of hemophilia, sickle cell disease and other genetic diseases. Further advancements in delivery systems, including lipid nanoparticles and engineered viral vectors were achieved. Refinements in clustered regularly interspaced short palindromic repeats-Cas9 and base-editing tools improved precision and reduced off-target effects, enabling new approaches for genetic disorders. Global collaboration underscored the collective effort to accelerate CGT progress. MSCs remain central to CGT research, focusing on their immunomodulatory properties and clinical applications in autoimmune diseases and graft-versus-host disease. Economic and policy landscapes evolved alongside scientific advancements. Record-breaking approvals and biotech IPOs underscored CGT's economic potential, while affordability and equitable access emerged as critical challenges. Regulatory agencies advanced harmonized guidelines for manufacturing and clinical evaluation, streamlining global access to these therapies. Ethical considerations, including the affordability of therapies and the need for diverse clinical trial representation, remained prominent. Despite progress, challenges persist in scalability, safety and regulatory harmonization. Manufacturing improvements are essential to meet growing demand, while addressing safety concerns, such as off-target gene-editing effects and tumorigenicity in MSC therapies, remains paramount.
2024年是细胞和基因治疗（CGT）的变革之年，在科学创新、监管审批和商业化里程碑方面取得了重大进展。本综述重点介绍了CGT的关键发展，包括嵌合抗原受体（CAR）-T疗法、间充质基质细胞（MSC）、基因编辑和再生医学的创新，以及在可扩展性、监管和安全性方面的挑战。CAR-T技术的显著突破将其应用范围从肿瘤学扩展到自身免疫性疾病，包括狼疮和系统性硬化症。基因疗法取得了重大里程碑，以治疗血友病、镰状细胞病和其他遗传疾病的监管批准为例。在递送系统方面取得了进一步进展，包括脂质纳米颗粒和工程化病毒载体。成簇规律间隔短回文重复序列-Cas9和碱基编辑工具的改进提高了精度并减少了脱靶效应，为遗传疾病带来了新的治疗方法。全球合作强调了加速CGT进展的集体努力。MSC仍然是CGT研究的核心，重点关注其免疫调节特性以及在自身免疫性疾病和移植物抗宿主病中的临床应用。经济和政策格局随着科学进步而演变。破纪录的批准和生物技术公司的首次公开募股凸显了CGT的经济潜力，而可负担性和公平可及性成为关键挑战。监管机构推进了制造和临床评估的统一指南，简化了全球对这些疗法的获取。伦理考量，包括疗法的可负担性和多样化临床试验代表性的需求，仍然十分突出。尽管取得了进展，但在可扩展性、安全性和监管协调方面仍然存在挑战。制造改进对于满足不断增长的需求至关重要，同时解决安全问题，如脱靶基因编辑效应和MSC疗法中的致瘤性，仍然至关重要。
