A nanobody-guided multifunctional T cell engager promotes strong anti-tumor responses via synergistic immuno-photothermal effects

纳米抗体引导的多功能 T 细胞接合器通过协同免疫光热效应促进强烈的抗肿瘤反应

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作者:Shenxia Xie #, Wei Shi #, Siliang Duan #, Xianing Huang, Aiqun Liu, Xiaoqiong Hou, Xuandong Lin, Dani Zhong, Shuyang Sun, Ziqiang Ding, Xiaomei Yang, Xiaoyuan Chen, Xiaoling Lu

Background

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.

Conclusions

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.

Results

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. Conclusions: 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.

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