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 improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.
Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.
癌症免疫治疗已显著推进了癌症治疗,在部分恶性肿瘤中实现了持久缓解。
癌症免疫治疗已显著推进了癌症治疗,在部分恶性肿瘤中实现了持久缓解。然而,其广泛应用受到重大挑战的限制:在许多实体瘤中疗效低下、严重的副作用,以及肿瘤微环境(TME)促进的免疫逃逸。纳米技术为解决这些障碍提供了一种有前景的方法。通过使用纳米颗粒(NPs),我们可以将治疗药物精准递送至肿瘤部位,确保控释以尽量减少副作用,并放大免疫反应,从而大幅提升免疫治疗的效果。本综述全面强调了利用纳米技术增强癌症免疫治疗的最新进展。本文详细介绍了纳米技术在该领域的各种应用。文中讨论了响应TME信号以直接在肿瘤处释放药物(例如检查点抑制剂)的智能纳米颗粒,从而减少全身副作用并激活T细胞。我们还探讨了纳米疫苗——其共同递送肿瘤标志物和免疫增强剂——如何诱导抗原特异性免疫反应。此外,负载mRNA的纳米颗粒可在体内直接改造CAR T细胞,简化治疗并提高疗效。文中还介绍了使用PLGA NPs递送IL-2等免疫增强剂的策略,这些策略在激活免疫细胞的同时将全身性问题降至最低。本综述还解释了纳米颗粒如何重编程免疫抑制性TME,以创造更有利于免疫作用的环境。我们还强调,纳米技术增强的过继性疗法,特别是细胞因子诱导的杀伤(CIK)细胞免疫疗法,在改善肿瘤靶向性、治疗持久性和整体抗癌疗效方面具有巨大潜力。总体而言,我们强调了纳米颗粒与化疗、放疗、光热/光动力疗法等其他治疗手段联合所实现的协同效应,这些效应可将难治性肿瘤转化为敏感靶点。纳米技术与免疫治疗的整合有望切实推动未来癌症治疗的发展。
Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effectiveness of immunotherapy. This review comprehensively highlights the latest advancements in using nanotechnology to enhance cancer immunotherapy. This paper details various applications of nanotech in this field. It discusses smart nanoparticles that respond to TME signals to release drugs (e.g., checkpoint inhibitors) directly at the tumor, reducing systemic side effects and activating T-cells. We also explore how nanovaccines, which co-deliver tumor markers and immune boosters, can induce antigen-specific immune responses. Furthermore, mRNA-loaded nanoparticles can directly modify CAR T-cells inside the body, simplifying treatment and increasing efficacy. Strategies like using PLGA NPs to deliver immune enhancers such as IL-2 are also presented, which activate immune cells while minimizing systemic issues. The review also explains how nanoparticles can re-engineer the immunosuppressive TME to create an environment more conducive to immune action. We also emphasize that nanotechnology-enhanced adoptive therapies, particularly cytokine-induced killer (CIK) cell immunotherapy, hold great potential to improve tumor targeting, treatment persistence durability, and overall anticancer efficacy. Collectively, we highlight synergistic effects achieved by combining nanoparticles with other treatments like chemotherapy, radiation, photothermal/photodynamic therapy, and more, which can turn hard-to-treat tumors into susceptible targets. The integration of nanotechnology and immunotherapy holds the potential to meaningfully advance future cancer therapy.
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