Universal endogenous antibody recruiting nanobodies capable of triggering immune effectors for targeted cancer immunotherapy.
Universal endogenous antibody recruiting nanobodies capable of triggering immune effectors for targeted cancer immunotherapy.
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通用内源性抗体募集纳米型，能够触发靶向癌症免疫疗法的免疫效应子。
DOI：
10.1039/d0sc05332e
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发表时间：
2021-02-11
期刊：
影响因子：
8.4
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Hong H;Li C;Gong L;Wang J;Li D;Shi J;Zhou Z;Huang Z;Wu Z
开发用于癌症免疫治疗的单克隆抗体（mab）既昂贵又复杂。与单克隆抗体相比，纳米抗体是一种具有良好药理特性的小抗体，但由于缺乏Fc区和较差的药代动力学，其抗癌功效有限。在这种背景下，工程通用内源性抗体招募纳米体（UEAR Nbs）作为一种通用且经济有效的方法被开发出来，以产生功能抗体样纳米体，可以重现Fc生物功能，用于癌症免疫治疗。UEAR Nbs由IgG结合域和纳米体组成，在大肠杆菌中重组表达，可以在体外募集内源性IgG到癌细胞表面，并引发有效的免疫应答，杀死癌细胞。此外，研究证明，UEAR Nbs在体内的半衰期明显改善。在EGFR阳性三阴性乳腺癌（TNBC）小鼠模型中证实了UEAR Nbs的体内抗肿瘤功效。通用内源性抗体招募纳米体（Universal endogenous antibody recruiting nanobodies, UEAR Nbs）由IgGs结合域和纳米体组成，可以将内源性IgGs重新定向到靶细胞表面，并在体外和体内引发有效的免疫应答，从而消灭癌细胞。
Developing monoclonal antibodies (mAbs) for cancer immunotherapy is expensive and complicated. Nanobodies are small antibodies possessing favorable pharmacological properties compared with mAbs, but have limited anticancer efficacy due to the lack of an Fc region and poor pharmacokinetics. In this context, engineered universal endogenous antibody-recruiting nanobodies (UEAR Nbs), as a general and cost-effective approach, were developed to generate functional antibody-like nanobodies that could recapitulate the Fc biological functions for cancer immunotherapy. The UEAR Nbs, composed of the IgG binding domain and nanobody, were recombinantly expressed in E. coli and could recruit endogenous IgGs onto the cancer cell surface and trigger potent immune responses to kill cancer cells in vitro. Moreover, it was proved that UEAR Nbs displayed significantly improved half-lives in vivo. The in vivo antitumor efficacy of UEAR Nbs was demonstrated in a murine model using EGFR positive triple-negative breast cancer (TNBC). Universal endogenous antibody recruiting nanobodies (UEAR Nbs), composed of IgGs binding domain and nanobody, could redirect endogenous IgGs onto target cell surfaces and evoke potent immune responses to eliminate cancer cells in vitro and in vivo.
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