工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
我们的方法将酶/前药治疗和免疫治疗整合到一个单一的细菌递送系统中,通过提供合理设计的空间控制化学免疫治疗框架,克服了传统疗法的关键局限性。
英文原题:Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade.
目前,癌症免疫治疗中的两个主要挑战通常阻碍了T细胞受体修饰T细胞(TCR-T)疗法在实体瘤治疗中的应用,包括T细胞浸润实体瘤组织的能力有限以及抑制T细胞抗肿瘤效能的免疫抑制信号。
目前,癌症免疫治疗中有两项主要挑战常限制T细胞受体修饰T细胞(TCR-T)疗法用于实体瘤:T细胞浸润实体瘤组织的能力有限,以及抑制T细胞抗肿瘤效能的免疫抑制信号。本研究构建了NY-ESO-1特异性TCR-T细胞,并引入聚乙二醇-磷脂(PEG-脂质),以非肽类九肽iRGD稳定修饰NY-ESO-1 TCR-T细胞,旨在增强其体内穿透能力;随后联合PD-1阻断以缓解免疫抑制信号。结果提示,以iRGD稳定修饰NY-ESO-1 TCR-T是一种简单有效的策略,可使TCR-T靶向并穿透实体瘤组织。此外,iRGD修饰的NY-ESO-1 TCR-T联合PD-1阻断,为治疗难治性NY-ESO-1阳性实体瘤提供了一种新的协同策略。
Currently, two main challenges in cancer immunotherapy commonly hinder the application of T cell receptor-modified T cell (TCR-T) therapy in the treatment of solid tumors, including the limited ability of T cells to infiltrate solid tumor tissues and the immunosuppressive signals that restrain the anti-tumor efficacy of T cells. In this study, we constructed NY-ESO-1-specific TCR-T and introduced polyethylene glycol-phospholipids (PEG-lipids) to stably modify NY-ESO-1 TCR-T with nonapeptide iRGD, aiming to enhance the penetrability of T cells in vivo, then we combined iRGD-modified NY-ESO-1 TCR-T (iRGD-NY-ESO-1 TCR-T) with PD-1 blockade to alleviate immunosuppressive signals. In result, it is suggested that stably modifying NY-ESO-1 TCR-T with iRGD is a simple and effective strategy to enable TCR-T to target and penetrate solid tumor tissues. Besides, the combination of iRGD-NY-ESO-1 TCR-T with PD-1 blockade presents a novel synergistic strategy for the treatment of refractory NY-ESO-1-positive solid tumors.
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