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:Advances in Nanotechnology for Lymphoma Treatment: Targeted Delivery, Immunomodulation, and TME-Responsive Therapy Strategies.
Advances in Nanotechnology for Lymphoma Treatment: Targeted Delivery, Immunomodulation, and TME-Responsive Therapy Strategies.
淋巴瘤是一种异质性淋巴细胞恶性增殖性疾病,兼具液体肿瘤和实体肿瘤的特征。
淋巴瘤是一种异质性淋巴细胞恶性增殖性疾病,兼具液体肿瘤和实体肿瘤的特征。随着靶向药物、单克隆抗体、双特异性抗体、抗体药物偶联物和CAR-T疗法的出现,淋巴瘤的治疗格局发生了转变。然而,这些疗法也存在局限性,如血浆循环时间短、生物利用度低、耐药性的产生以及剂量依赖性毒性。随着纳米技术的进步,基于纳米技术的靶向递送系统能够实现肿瘤特异性靶向并减少脱靶毒性。纳米免疫治疗系统,如基于纳米抗体的CAR-T疗法和mRNA-LNP纳米疫苗,解决了抗原逃逸导致的耐药和复发等局限性,诱导长期抗肿瘤免疫。此外,响应肿瘤微环境(TME)的智能设计可以显著增强药物在病灶部位的蓄积和释放效率。基于纳米技术的创新疗法正逐步从实验室走向临床。通过设计靶向纳米载体、纳米免疫疗法和TME响应性智能纳米治疗平台,可以实现抗淋巴瘤药物的靶向递送,提高疗效并降低毒性。同时,这些平台可以整合多种治疗模式(如化学动力学治疗、免疫调节和基因沉默),实现协同增强的抗淋巴瘤效果,为淋巴瘤治疗提供新范式。
Lymphoma is a heterogeneous malignant proliferative disease of lymphocytes, with characteristics of liquid tumor and solid tumor. With the emergence of targeted drugs, monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and CAR-T therapy, the treatment landscape for lymphoma has been transformed. However, these therapies also possess limitations such as short plasma circulation time, low bioavailability, the development of drug resistance, and dose-dependent toxicity. With the advancement of nanotechnology, nanotech-based targeted delivery systems enable tumor-specific targeting and reduce off-target toxicity. Nano-immunotherapeutic systems, such as nanobody-based CAR-T therapy and mRNA-LNP nanovaccines, address limitations like drug resistance and relapse caused by antigen escape, inducing long-term anti-tumor immunity. Furthermore, smart designs responsive to the tumor microenvironment (TME) can significantly enhance drug accumulation and release efficiency at the lesion site. Innovative nanotech-based therapies are progressively transitioning from the laboratory to the clinic. By designing targeted nanocarriers, nano-immunotherapies, and TME-responsive intelligent nanotherapeutic platforms, targeted delivery of anti-lymphoma drugs can be achieved, enhancing efficacy and reducing toxicity. Simultaneously, these platforms can integrate multiple therapeutic modalities (such as chemodynamic therapy, immunomodulation, and gene silencing) to achieve synergistic and enhanced anti-lymphoma effects, offering new paradigms for lymphoma treatment.
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