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:From CAR-T Cells to Exosome-Based Immunotherapy: Exploring the Frontiers of Cell-Free Targeted Cancer Therapeutics.
嵌合抗原受体(CAR)细胞疗法通过实现靶向且强效的抗肿瘤免疫应答,彻底改变了肿瘤免疫治疗。
嵌合抗原受体(CAR)细胞疗法通过实现靶向且强效的抗肿瘤免疫应答,革新了癌症免疫治疗。然而,实体瘤疗效有限、细胞因子释放综合征(CRS)等严重毒性以及生产复杂性,限制了其更广泛应用。近期,CAR细胞来源外泌体(CAR-Exo)作为有前景的无细胞治疗替代方案出现;它们保留母细胞关键抗肿瘤功能,同时可能克服活细胞疗法的局限。这些纳米级囊泡可递送具有生物活性的CAR分子、细胞毒蛋白及免疫调节载荷,实现靶向杀伤肿瘤、降低全身毒性,并具备“现货型”应用潜力。本综述全面探讨源自T细胞、自然杀伤(NK)细胞及其他免疫效应细胞的CAR-Exo生物学、工程化和治疗潜力。文章讨论分离、表征和载荷分析技术进展,以及支持其应用的临床前和早期临床数据;并探讨规模化生产、生物分布及肿瘤微环境中免疫逃逸等转化挑战。细胞和外泌体CAR平台结合有望提高癌症治疗的疗效与安全性,代表靶向免疫治疗的前沿方向。
Chimeric antigen receptor (CAR) cell therapies have revolutionized cancer immunotherapy by enabling targeted and potent antitumor immune responses. However, clinical challenges such as limited efficacy in solid tumors, severe toxicities including cytokine release syndrome (CRS), and manufacturing complexities restrict their broader use. Recently, CAR cell-derived exosomes (CAR-Exos) have emerged as promising cell-free therapeutic alternatives that retain the key antitumor functionalities of their parent cells while potentially overcoming the limitations of live cellular therapies. These nanoscale vesicles can deliver bioactive CAR molecules, cytotoxic proteins, and immunomodulatory cargo, enabling targeted tumor cell killing with reduced systemic toxicity and offering "off-the-shelf" applicability. This review comprehensively explores the biology, engineering, and therapeutic potential of CAR-Exos derived from T cells, natural killer (NK) cells, and other immune effectors. We discuss advances in isolation, characterization, and cargo profiling techniques, as well as preclinical and early clinical data supporting their application. Further, we address translational challenges including large-scale production, biodistribution, and immune evasion in tumor microenvironments. Combining cellular and exosomal CAR platforms holds promise to enhance efficacy and safety in cancer treatment, representing a frontier in targeted immunotherapy.
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