肿瘤细胞治疗研究
英文原题：Engineering an in vivo charging station for CAR-redirected invariant natural killer T cells to enhance cancer therapy.
恒定自然杀伤T（iNKT）细胞是T淋巴细胞的一个独特亚群，具有同种异体潜力及强大的实体瘤归巢能力，使其在癌症免疫治疗中具有吸引力。
恒定自然杀伤T（iNKT）细胞是T淋巴细胞的一个独特亚群，具有异体反应潜力和强大的实体瘤归巢能力，使其在癌症免疫治疗中具有吸引力。与传统T细胞不同，iNKT细胞识别由非多态性CD1d分子呈递的脂质抗原。嵌合抗原受体（CAR）重定向的iNKT（CAR-iNKT）细胞已显示出前景；然而，其临床疗效受到肿瘤微环境中激活不足和长期持久性差的限制。在此，我们描述了iNKT细胞靶向微粒招募与激活系统（iMRAS），这是一个仿生平台，旨在在体内局部招募、激活和扩增CAR-iNKT细胞。作为体内“充电站”，iMRAS提供趋化和激活信号，增强CAR-iNKT细胞功能，改善临床前淋巴瘤和黑色素瘤模型中的持久性和肿瘤控制。通过其仿生设计和局部免疫刺激效应，iMRAS有助于克服当前实体瘤治疗的局限性，为推进基于CAR-iNKT细胞的癌症免疫治疗建立了一个稳健的平台。
Invariant natural killer T (iNKT) cells are a unique subset of T lymphocytes with allogeneic potential and strong solid tumour-homing capacity, making them attractive for cancer immunotherapy. Unlike conventional T cells, iNKT cells recognize lipid antigens presented by the non-polymorphic CD1d molecule. Chimaeric antigen receptor (CAR)-redirected iNKT (CAR-iNKT) cells have shown promise; however, their clinical efficacy is limited by insufficient activation and poor long-term persistence within the tumour microenvironment. Here we describe the iNKT cell-targeted microparticle recruitment and activation system (iMRAS), a biomimetic platform engineered to locally recruit, activate and expand CAR-iNKT cells in vivo. Acting as an in vivo 'charging station', iMRAS provides chemotactic and activating cues that enhance CAR-iNKT cell functionality, improving persistence and tumour control in preclinical lymphoma and melanoma models. Through its biomimetic design and localized immunostimulatory effects, iMRAS helps overcome the limitations of current therapies for solid tumours, establishing a robust platform for advancing CAR-iNKT cell-based cancer immunotherapy.
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