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将工程化自体 T 细胞作为治疗实体瘤的药物进行产业化。

Industrializing engineered autologous T cells as medicines for solid tumours.

机构信息

Oncology R&D, GlaxoSmithKline, Stevenage, UK.

Immatics Biotechnologies, Munich, Germany.

出版信息

Nat Rev Drug Discov. 2021 Jun;20(6):476-488. doi: 10.1038/s41573-021-00175-8. Epub 2021 Apr 8.

Abstract

Cell therapy is one of the fastest growing areas in the pharmaceutical industry, with considerable therapeutic potential. However, substantial challenges regarding the utility of these therapies will need to be addressed before they can become mainstream medicines with applicability similar to that of small molecules or monoclonal antibodies. Engineered T cells have achieved success in the treatment of blood cancers, with four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies based on their unprecedented efficacy in clinical trials. However, similar results have not yet been achieved in the treatment of the much larger patient population with solid tumours. For cell therapies to become mainstream medicines, they may need to offer transformational clinical effects for patients and be applicable in disease settings that remain unaddressed by simpler approaches. This Perspective provides an industry perspective on the progress achieved by engineered T cell therapies to date and the opportunities and current barriers for accessing broader patient populations, and discusses the solutions and new development strategies required to fully industrialize the therapeutic potential of engineered T cells as medicines.

摘要

细胞疗法是制药行业发展最快的领域之一,具有相当大的治疗潜力。然而,在这些疗法成为与小分子或单克隆抗体具有相似适用性的主流药物之前,还需要解决实质性的应用问题。经过基因工程改造的 T 细胞在治疗血液癌症方面取得了成功,目前已有四种嵌合抗原受体(CAR)-T 细胞疗法因在临床试验中具有前所未有的疗效而被批准用于治疗 B 细胞恶性肿瘤。然而,在治疗数量庞大得多的实体瘤患者方面,尚未取得类似的效果。为了使细胞疗法成为主流药物,它们可能需要为患者提供变革性的临床效果,并适用于更简单方法无法解决的疾病治疗环境。本文从行业角度介绍了基因工程改造的 T 细胞疗法迄今取得的进展,以及扩大患者群体的机会和当前障碍,并讨论了充分实现基因工程改造的 T 细胞作为药物的治疗潜力所需的解决方案和新的开发策略。

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