Guangxi Key Laboratory of Nanobody Research, Guangxi Nanobody Engineering Research Center, College of Stomatology, Hospital of Stomatology Guangxi Medical University, Nanning, Guangxi, 530021, P. R. China.
Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, 530021, P. R. China.
J Nanobiotechnology. 2024 Sep 14;22(1):561. doi: 10.1186/s12951-024-02781-1.
T cell-based immunotherapies are facing great challenges in the recruitment and activation of tumor-specific T cells against solid tumors. Among which, utilizing nanobody (Nb) or nanobodies (Nbs) to construct T cell engager has emerged as a more practical potential for enhancing the anti-tumor effectiveness of T cells. Here, we designed a new Nb-guided multifunctional T cell engager (Nb-MuTE) that not only recruited effector T cells into the tumor tissues, but also efficiently activated T cells anti-tumor immunity when synergies with photothermal effect.
The Nb-MuTE, which was constructed based on an indocyanine green (ICG)-containing liposome with surface conjugation of CD105 and CD3 Nbs, and showed excellent targetability to both tumor and T cells, following enhancement of activation, proliferation and cytokine secretion of tumor-specific T cells. Notably, the immunological anti-tumor functions of Nb-MuTE-mediated T cells were further enhanced by the ICG-induced photothermal effect in vitro and in vivo.
Such a new platform Nb-MuTE provides a practical and "all-in-one" strategy to potentiate T cell responses for the treatment of solid tumor in clinic.
T 细胞为基础的免疫疗法在募集和激活针对实体瘤的肿瘤特异性 T 细胞方面面临巨大挑战。其中,利用纳米抗体(Nb)或纳米抗体(Nbs)构建 T 细胞衔接器已成为增强 T 细胞抗肿瘤效果的一种更实用的潜力。在这里,我们设计了一种新的纳米抗体引导的多功能 T 细胞衔接器(Nb-MuTE),它不仅可以募集效应 T 细胞进入肿瘤组织,而且在与光热效应协同作用时还可以有效地激活 T 细胞抗肿瘤免疫。
Nb-MuTE 是基于含有吲哚菁绿(ICG)的脂质体构建的,表面连接有 CD105 和 CD3 Nbs,对肿瘤和 T 细胞均具有优异的靶向性,可增强肿瘤特异性 T 细胞的激活、增殖和细胞因子分泌。值得注意的是,ICG 诱导的光热效应对 Nb-MuTE 介导的 T 细胞的免疫抗肿瘤功能具有进一步的增强作用,无论是在体外还是体内。
这种新的平台 Nb-MuTE 为临床治疗实体瘤提供了一种实用的“一体化”策略,以增强 T 细胞的反应。