决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Incorporating mRNA therapeutics into biological treatments of hematologic malignancies.
近期mRNA技术的进步为治疗血液系统恶性肿瘤开辟了新的治疗途径,为增强现有免疫疗法提供了创新方法。
mRNA技术的最新进展为治疗血液系统恶性肿瘤开辟了新的治疗途径,为增强现有免疫疗法提供了创新方法。本综述探讨了基于体外转录(IVT)-mRNA的平台在血液肿瘤学中日益扩大的作用,重点关注以下关键领域:单克隆抗体生产、双特异性抗体开发和CAR-T细胞工程。与传统生物制剂不同,mRNA允许治疗性蛋白在体内表达,降低了生产复杂性,并通过可扩展的无细胞合成扩大了可及性。IVT-mRNA编码的单克隆抗体和双特异性抗体可以克服半衰期短和需要持续输注等局限性,同时实现Fc沉默、蛋白酶激活掩蔽和组合免疫疗法等创新。在CAR-T细胞治疗中,IVT-mRNA提供了瞬时、更安全的替代方案来取代基于病毒载体的方法,并促进了新兴策略,如体内CAR编程和IVT-mRNA疫苗样加强针。尽管有这些优势,挑战仍然存在,包括递送精确性、治疗效果的持久性以及有限的临床试验成功率。除治疗机制外,生物信息学和AI在IVT-mRNA设计中的整合正在加速个性化和高效癌症治疗的开发。总体而言,mRNA技术正在重新定义血液学中的免疫治疗,并具有扩大全球先进治疗可及性的潜力。
The recent advancement of mRNA technology has opened new therapeutic avenues for treating hematologic malignancies, offering innovative approaches to enhance existing immunotherapies. This review examines the expanding role of in vitro transcribed (IVT)-mRNA-based platforms in hemato-oncology, focusing on key areas: monoclonal antibody production, bispecific antibody development, and CAR-T cell engineering. Unlike conventional biologics, mRNA allows for in vivo expression of therapeutic proteins, reducing manufacturing complexity and expanding access through scalable, cell-free synthesis. IVT-mRNA-encoded monoclonal and bispecific antibodies can overcome limitations such as short half-life and the need for continuous infusion, while enabling innovations like Fc silencing, protease-activated masking, and combinatorial immunotherapies. In CAR-T cell therapy, IVT-mRNA provides transient, safer alternatives to viral vector-based approaches and facilitates emerging strategies such as in vivo CAR programming and IVT-mRNA vaccine-like boosters. Despite these advantages, challenges remain, including delivery precision, durability of therapeutic effects, and limited clinical trial success. Beyond therapeutic mechanisms, the integration of bioinformatics and AI in IVT-mRNA design is accelerating the development of personalized and efficient cancer treatments. Overall, mRNA technology is redefining immunotherapy in hematology and holds the potential to broaden access to advanced treatments globally.
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