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2025年8月22日至23日,由中国北京健康促进会与广州市红棉肿瘤和罕见病公益基金会联合主办、北京陆道培血液病研究院承办的第十三届陆道培血液病学术大会在京隆重召开。本次会议汇集全球顶尖血液学专家,聚焦造血干细胞移植、细胞治疗、血液肿瘤精准诊疗等核心议题,为千余名参会者呈现了一场高规格、深层次的学术盛宴。会议期间,新加坡总医院Francesca Lorraine Wei Inng Lim教授分享了“新加坡细胞治疗全景(Cell Therapy Landscape in Singapore)”的精彩报告。《肿瘤瞭望-血液时讯》特邀Francesca Lorraine Wei Inng Lim教授围绕核心问题展开深入对话,以期为优化细胞治疗领域提供重要的实践指导与理论参考。
PART.1
新加坡近年在细胞与基因治疗(CGT)方面发展迅速。请问您如何评估目前新加坡在临床可及性、本地制造能力与监管框架三者之间的平衡?未来最关键的瓶颈是什么?
Francesca Lorraine Wei Inng Lim教授:我认为新加坡在细胞与基因治疗领域的发展机遇得天独厚。我们系统吸收了美国、欧洲乃至中国的先进经验,但必须承认当前全球细胞与基因治疗领域的技术主导力量仍集中在这些传统强国。基于此,我国临床团队已建立完善的国际化培训体系——多名临床医生被派往MD安德森癌症中心、纽约纪念斯隆凯特琳癌症中心、伦敦国王学院等全球顶尖CAR-T治疗中心进修,护理团队同样接受标准化培训,确保细胞治疗产品能够安全规范地应用于患者。
在硬件设施层面,新加坡国家级GMP平台已具备充足产能,新建的ACTRIS设施作为大型多功能生产中心,可同步处理多种细胞治疗产品,这得益于政府前瞻性的政策支持。现行的双证体系(生产许可证+GMP证书)为产品质量提供了制度保障,基础设施层面已不存在实质性障碍。
监管框架方面,正如我在本次演讲中所述,新加坡的法规体系正随着技术发展持续完善。我们已建立明确的指导文件,确保创新细胞与基因治疗产品的引进、转化及临床应用全过程符合质量安全要求。当前患者获取创新疗法的途径较以往更趋灵活,但未来技术升级带来的挑战不容忽视——例如诱导多能干细胞(iPSC)技术深化应用后,如何建立新型产品的质量控制标准和临床放行准则,将成为监管机构与临床医生共同面临的重大课题。
特别需要关注的是,当这些前沿疗法应用于罹患侵袭性血液系统恶性肿瘤的危重患者时,必须严格评估其潜在风险。我们尚未完全掌握新型细胞治疗产品的长期副作用谱系,这要求临床团队必须保持高度谨慎,避免对患者造成额外伤害。此外,高昂的治疗成本仍是制约患者可及性的关键因素,若产品定价持续维持在数十万美元区间,即便具有救命价值,其临床推广仍将面临伦理困境。
值得强调的是,这些挑战并非全新课题,而是我们在CAR-T疗法临床应用过程中已积累的实践经验。核心团队需持续整合既有知识体系,将应对CAR-T疗法的成熟经验有效迁移至其他创新疗法,这种技术迭代与知识传承的闭环机制,正是推动新加坡成为区域细胞治疗中心的关键驱动力。
(上下滑动查看英文原文)
Singapore has seen rapid growth in cell and gene therapy. How do you assess the balance today between clinical access, local GMP manufacturing capacity, and the regulatory framework? What do you see as the single biggest bottleneck over the next years?
Pro.Francesca Lorraine Wei Inng Lim:Singapore is in a notably advantageous position in the field of cell and gene therapy. We have gained substantial insights from leading regions including the United States, Europe, and China, which are currently the major powerhouses in this domain. To enhance local expertise, several of our clinicians have been sent to specialized international centers with significant experience in CAR-T therapy, such as MD Anderson, Memorial Sloan Kettering in New York, and King’s College in the UK. Consequently, both our medical and nursing staff are well-trained to administer cell-based therapies safely and effectively.
In addition, Singapore has established a robust national GMP facility, which now possesses considerable capacity for local manufacturing. Although newly established, ACTRIS is a large-scale facility capable of simultaneous production of multiple cell therapy products. This initiative, supported by the government, provides a fully licensed and GMP-certified infrastructure, thereby alleviating potential manufacturing constraints.
Regarding regulatory frameworks, Singapore’s guidelines are continually evolving. Clear guidance documents are available to facilitate the safe and quality-assured translation of cell and gene therapies from bench to bedside. This regulatory maturation is critical for sustaining progress in the field.
However, several challenges lie ahead. As technologies advance—for instance, with the use of induced pluripotent stem cells (iPSCs) and their subsequent genetic modification—questions arise concerning quality control, safety profiling, and appropriate release criteria for clinical application. These challenges extend beyond regulatory bodies to clinicians themselves, especially when treating critically ill patients with aggressive malignancies. The potential side effects of novel therapies must be thoroughly evaluated to avoid additional harm.
Furthermore, the high cost of these treatments remains a significant barrier. With prices ranging into the hundreds of thousands of dollars, patient accessibility becomes a pressing concern even for life-saving interventions.
It is important to recognize that these challenges are not entirely new; many have already been encountered with CAR-T therapy in Singapore. Therefore, a collaborative and proactive approach—leveraging existing knowledge and experience—is essential to address these bottlenecks and facilitate the application of current learnings to other emerging therapeutic avenues.
PART.2
新加坡作为区域中心,有“hub-and-spoke”跨境合作的先例以扩大 CAR-T 可及性。请问在伦理审查、患者迁移与长期随访方面,您遇到过哪些实际挑战?对想采用类似模式的邻国或中心,您有哪些政策或资源配置上的建议?
Francesca Lorraine Wei Inng Lim教授:新加坡中央医院在移植项目中采用"中心-辐射"模式已有较长历史。我们曾为越南等地的白血病和淋巴瘤患者实施骨髓移植治疗,术后患者通常返回原籍国,由当地血液科医生继续管理。基于这一经验,我们在开展CAR-T治疗项目时构建了类似体系:海外患者(如印度、越南)可直接来我院就诊,或由其原籍国医师通过临床渠道与我们团队对接病例。但病例讨论仅是流程的首要环节,后续必须经多学科会诊(MDT)形成治疗共识,即由肿瘤专家、移植团队、细胞治疗组、重症医学科及感染科医师共同参与的联合诊疗会议,对病例进行公开评估,以决定是否接收该海外患者。
尤为关键的是,转诊国需建立持续管理患者的能力,确保其返国后仍能获得规范治疗。现代通讯技术(如Zoom、Microsoft Teams)显著改善了医患沟通效率,相较以往依赖电子邮件可能造成的延迟,实时视频会议使联合门诊成为可能——我院医师与海外医生可同步查看患者情况,实现全流程无缝管理。
对于参与临床试验的患者,其伦理审查流程已较为成熟。但若患者因无其他治疗选择而寻求创新疗法,则必须通过医院伦理委员会的严格审核,确保患者充分理解治疗风险、获益及伦理考量,保障创新挽救性治疗的安全实施。我们尤其注重避免患者跨境治疗后出现严重并发症甚至死亡的情况,这是医患双方均不愿见到的最差结局。通过整合既有经验与技术升级,我院正不断完善"中心-辐射"模式的支持体系,以实现细胞治疗的安全推广与规范应用。
(上下滑动查看英文原文)
Singapore has served as a regional hub with a “hub-and-spoke” model to expand CAR-T access. What practical challenges have you faced regarding ethics review, patient movement, and long-term follow-up? What policy or resource-allocation advice would you give centers or neighboring countries seeking to adopt a similar model?
Pro.Francesca Lorraine Wei Inng Lim:The hub-and-spoke model has been an integral part of our transplant program at Singapore General Hospital for a considerable time. For instance, we have regularly managed patients from Vietnam seeking bone marrow transplantation for leukemias and lymphomas in Singapore, with subsequent follow-up care coordinated with their local hematologists upon return to their home country.
Similarly, with the initiation of our CAR-T therapy program, we adopted an analogous framework. This allows patients to directly contact our center or be referred by their physicians from overseas, such as from India or Vietnam, for clinical discussion. However, such inquiries represent only the initial step. Each case must undergo formal review by our multidisciplinary tumor board, which includes disease specialists, transplant and cell therapy team members, intensivists, and infectious disease experts. This collaborative evaluation determines our capacity to provide care for international patients in Singapore.
Of paramount importance is ensuring that referring centers can continue management after the patient returns home. Advances in telecommunication—such as Zoom and Microsoft Teams—have significantly improved coordination compared to earlier reliance on email, which often incurred delays. We now emphasize structured virtual joint clinics to enable real-time consultation between our team and overseas physicians, ensuring seamless continuity of care throughout the treatment process.
For patients entering Singapore under clinical trials, ethical oversight is inherently addressed within trial protocols. However, those seeking experimental therapies outside of trials must obtain approval from our institutional ethics committee. This ensures full comprehension of the risks, benefits, and ethical implications involved in receiving innovative salvage therapies. Our utmost priority is to avoid adverse outcomes, such as clinical deterioration or death during their stay in Singapore, both for the well-being of the patients and in maintaining collaborative trust with international partners. This comprehensive and ethically grounded approach underpins our support of the hub-and-spoke model.
PART.3
展望未来,您如何看待新加坡在“从临床试验到商业化,以及推动国产化细胞治疗产品”这条路上的角色?在科研、产业与政府三方协作上,您最希望看到哪些具体举措来加速安全且公平的患者受益?
Francesca Lorraine Wei Inng Lim教授:对于学术界医师而言,将自主研发产品推进至注册上市及市场推广阶段存在显著挑战,单凭学术力量难以完成全流程运作,产业合作伙伴的参与至关重要。行业伙伴不仅能够提供市场准入及商业化推广的核心支持,更可通过规模化生产能力提升治疗产品的全球可及性,使新加坡本土研发成果惠及更广泛患者群体。
鉴于新加坡本土人口规模仅约六百万,开展超大型单中心临床试验存在现实限制,需采用多中心或跨国合作模式——以新加坡为核心基地,联合马来西亚、越南等邻国乃至中国开展协同研究,通过积累高质量多中心数据为产品注册提供依据,进而实现产品在亚太地区的战略布局。这一过程需构建学术界、产业界与监管机构的深度协作机制,辅以政策支持,方能形成从基础研究到临床应用的全链条创新转化体系。
(上下滑动查看英文原文)
Looking ahead, how do you envision Singapore’s role in moving cell therapies from trials to commercialization and in fostering domestically developed cell therapy products? In collaboration between academia, industry and government, what concrete measures would you most like to see to speed safe and equitable patient benefit?
Pro.Francesca Lorraine Wei Inng Lim:For physicians in academia, navigating the path to registration, commercialization, and broad distribution of a novel product presents significant challenges. This process is highly complex and cannot be undertaken alone, necessitating strategic collaborations with industry partners. Such partnerships are critically important, as industry involvement provides essential support in marketing, market entry, and scaling production capabilities to deliver the therapy to patients not only in Singapore but also worldwide.
Given Singapore’s relatively small population of just over six million, conducting large-scale clinical trials domestically is particularly difficult. A multi-center or regional approach—conducting trials in Singapore while also engaging neighboring countries such as Malaysia, Vietnam, or through collaborations with China—is often required. Generating robust clinical data through such international efforts enables subsequent regulatory filing and facilitates distribution across the Asia-Pacific region.
Therefore, collaboration between academia, researchers, and industry, supported by clear regulatory frameworks and government backing, is essential to overcoming these barriers and advancing innovative therapies to market.
(来源:《肿瘤瞭望–血液时讯》编辑部)
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