Smart MAnufactuRing for Autologous Cell ThERapies enabled by innovative biomonitoring technologies and advanced process control (SMARTER)

自体免疫疗法彻底改变了癌症治疗，为血癌患者提供了令人印象深刻的生存益处。使用肿瘤浸润淋巴细胞（TIL）的下一代个性化免疫疗法旨在克服CAR-T疗法在治疗实体瘤方面的疗效限制。缺乏有效、快速、自适应、可控和可扩展的制造工艺仍然是临床采用这种复杂的个性化细胞疗法的关键瓶颈之一。在SMARTER项目中，Achilles Therapeutics UK Limited是一家开发自体细胞疗法的临床阶段公司，与细胞和基因治疗弹射器卓越中心以及过程生物标志物发现（Instituto de Investigation Sanitaria La Fe）和生物过程传感器开发（Leibniz Universitas汉诺威）的学术专家合作。该联盟旨在为个性化自体细胞疗法开发一流的智能生物加工制造平台，首次实施在线过程分析技术和智能过程控制系统。该项目利用了新的T细胞扩增过程生物标志物的突破性发现，并开发了新的荧光光谱传感器，用于实时监测关键工艺参数，以实现精确TIL生物制造过程的自适应过程控制。项目完成后，原型研发平台将为GMP环境下商业规模生物反应器的后续开发做好准备。SMARTER平台将极大地提高生产效率，降低整体商品成本，缩短制造周期时间（缩短静脉到静脉的时间），减少批次故障，并使细胞治疗产品质量更加一致和可预测。最后，这些创新将使临床实施潜在的突破性个性化过继细胞疗法，用于治疗最难治疗的实体瘤，如肺癌和黑色素瘤。

Autologous immunotherapies have revolutionised cancer treatment providing impressive survival benefits in patients with blood cancers. The next generation of personalised immunotherapies using tumour-infiltrating lymphocytes (TIL) aims to overcome efficacy limitations of CAR-T therapies in the treatment of solid tumours. Lack of effective, fast, adaptive, controllable, and scalable manufacturing process remains one of the critical bottlenecks for clinical adoption of such complex personalised cell therapies. In the SMARTER project, Achilles Therapeutics UK Limited, a clinical-stage company developing autologous cell therapies, partners with the centre of excellence for Cell and Gene Therapy Catapult and academic experts in process biomarker discovery (Instituto de Investigation Sanitaria La Fe) and bioprocess sensor development (Leibniz Universitas Hannover). The consortium aims to develop a first-in-class, smart bioprocessing manufacturing platform for personalised autologous cell therapies, implementing for the first time in-line process analytical technologies and smart process control systems. The project exploits breakthrough discoveries of novel T cell expansion process biomarkers and development of new fluorescence spectroscopy sensors for real-time monitoring of critical process parameters, toa enable adaptive process control of the precision TIL biomanufacturing process. After the project, the prototype R&D platform will be ready for follow-up development of the commercial scale bioreactor in GMP environment. The SMARTER platform will critically improve production efficiency, reduce overall costs-of-goods, shorten manufacturing cycle times (shorter vein-to-vein time), decrease batch failures and lead to more consistent and predictable cell therapy product quality. Finally, the innovations will enable clinical implementation of a potential breakthrough personalised adoptive cell therapy for hardest-to-treat solid tumours such as lung cancer and melanoma.