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:Emerging advantages of nano delivery systems in enhancing CAR-T/CRISPR-Cas9 mediated cancer therapeutics.
病毒载体长期以来一直是癌症免疫治疗的核心,尤其是用于体外嵌合抗原受体(CAR)-T 细胞工程和癌症疫苗开发。
病毒载体长期以来一直是癌症免疫治疗的核心,特别是在体外嵌合抗原受体(CAR)-T细胞工程和癌症疫苗开发中。尽管取得了成功,但临床转化仍受限于免疫原性、插入突变、载荷容量受限和高生产成本。这些缺陷不仅损害安全性,还阻碍可扩展性和重复给药,而这两者对于持久的癌症控制至关重要。为了克服这些障碍,非病毒纳米载体系统已成为通用且更安全的替代方案。脂质纳米颗粒、聚合物平台、仿生外泌体样囊泡和水凝胶基系统能够实现核酸、免疫调节剂和化疗药物的靶向和控释递送,具有增强的稳定性、降低的全身毒性和改善的生物相容性。除了被动递送之外,这些智能纳米载体还可以通过肿瘤靶向配体、免疫检查点调节剂或刺激响应释放机制进行工程化改造,以重编程肿瘤微环境并增强T细胞和树突状细胞的激活。此外,纳米技术的模块化促进了多种治疗剂的共同递送,包括抗原、佐剂和检查点抑制剂,从而实现协同免疫治疗结果。最近在脂质纳米颗粒基mRNA疫苗的大规模制造和临床转化方面的进展,突显了这些系统在肿瘤学应用中的可行性。随着癌症免疫治疗向个性化和联合方案发展,纳米生物技术提供了一个变革性平台来替代传统病毒载体,推动更安全、更有效且临床可扩展的治疗。
Viral vectors have long been central to cancer immunotherapy, particularly for ex vivo chimeric antigen receptor (CAR)-T cell engineering and cancer vaccine development. Despite their success, clinical translation remains limited by immunogenicity, insertional mutagenesis, restricted cargo capacity, and high production costs. These drawbacks not only compromise safety but also hinder scalability and repeated dosing, both of which are critical for durable cancer control. To overcome these barriers, non-viral nanocarrier systems have emerged as versatile and safer alternatives. Lipid nanoparticles, polymeric platforms, biomimetic exosome-like vesicles, and hydrogel-based systems enable targeted and controlled delivery of nucleic acids, immunomodulators, and chemotherapeutics with enhanced stability, reduced systemic toxicity, and improved biocompatibility. Beyond passive delivery, these smart nanocarriers can be engineered with tumor-targeting ligands, immune checkpoint modulators, or stimulus-responsive release mechanisms to reprogram the tumor microenvironment and potentiate T-cell and dendritic cell activation. Furthermore, the modularity of nanotechnology facilitates co-delivery of multiple therapeutic agents, including antigens, adjuvants, and checkpoint inhibitors, allowing synergistic immunotherapeutic outcomes. Recent advances in large-scale manufacturing and clinical translation of lipid nanoparticle-based mRNA vaccines underscore the feasibility of these systems for oncology applications. As cancer immunotherapy evolves toward personalization and combination regimens, nanobiotechnology offers a transformative platform to replace conventional viral vectors, advancing safer, more effective, and clinically scalable treatments.
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