Buckland Karen F, Bobby Gaspar H
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom; Cellular Therapies, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom; Department of Clinical Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
Adv Drug Deliv Rev. 2014 Jun;73(100):162-9. doi: 10.1016/j.addr.2014.02.010. Epub 2014 Feb 28.
The range of possible gene and cell therapy applications is expanding at an extremely rapid rate and advanced therapy medicinal products (ATMPs) are currently the hottest topic in novel medicines, particularly for inherited diseases. Paediatric patients stand to gain enormously from these novel therapies as it now seems plausible to develop a gene or cell therapy for a vast number of inherited diseases. There are a wide variety of potential gene and cell therapies in various stages of development. Patients who received first gene therapy treatments for primary immune deficiencies (PIDs) are reaching 10 and 15 years post-treatment, with robust and sustained immune recovery. Cell therapy clinical trials are underway for a variety of tissues including corneal, retinal and muscle repair and islet cell transplantation. Various cell therapy approaches are also being trialled to enhance the safety of bone marrow transplants, which should improve survival rates in childhood cancers and PIDs. Progress in genetic engineering of lymphocyte populations to target and kill cancerous cells is also described. If successful these ATMPs may enhance or replace the existing chemo-ablative therapy for several paediatric cancers. Emerging applications of gene therapy now include skin and neurological disorders such as epidermolysis bullosa, epilepsy and leukodystrophy. Gene therapy trials for haemophilia, muscular dystrophy and a range of metabolic disorders are underway. There is a vast array of potential advanced therapy medicinal products (ATMPs), and these are likely to be more cost effective than existing medicines. However, the first clinical trials have not been without setbacks and some of the key adverse events are discussed. Furthermore, the arrival of this novel class of therapies brings many new challenges for the healthcare industry. We present a summary of the key non-clinical factors required for successful delivery of these potential treatments. Technological advances are needed in vector design, raw material manufacture, cell culture and transduction methodology, and particularly in making all these technologies readily scalable.
基因和细胞疗法的潜在应用范围正在以极快的速度扩展，先进治疗医药产品（ATMPs）目前是新药领域最热门的话题，尤其是对于遗传性疾病。儿科患者有望从这些新型疗法中大幅受益，因为现在为大量遗传性疾病开发基因或细胞疗法似乎是可行的。有各种各样处于不同开发阶段的潜在基因和细胞疗法。接受原发性免疫缺陷（PIDs）首次基因治疗的患者已治疗10至15年，免疫功能实现了强劲且持续的恢复。针对包括角膜、视网膜和肌肉修复以及胰岛细胞移植在内的多种组织的细胞疗法临床试验正在进行。还在试验各种细胞疗法以提高骨髓移植的安全性，这有望提高儿童癌症和原发性免疫缺陷疾病的生存率。文中还描述了淋巴细胞群体基因工程在靶向和杀死癌细胞方面的进展。如果成功，这些先进治疗医药产品可能会增强或取代几种儿科癌症现有的化学消融疗法。基因疗法的新兴应用现在包括皮肤和神经系统疾病，如大疱性表皮松解症、癫痫和脑白质营养不良。血友病、肌肉萎缩症和一系列代谢紊乱的基因疗法试验正在进行。有大量潜在的先进治疗医药产品，而且这些产品可能比现有药物更具成本效益。然而，首批临床试验并非没有挫折，文中讨论了一些关键的不良事件。此外，这类新型疗法的出现给医疗行业带来了许多新挑战。我们总结了成功提供这些潜在治疗所需的关键非临床因素。在载体设计、原材料制造、细胞培养和转导方法方面需要技术进步，特别是要使所有这些技术易于扩大规模。
