Universal endogenous antibody recruiting nanobodies capable of triggering immune effectors for targeted cancer immunotherapy |
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| Authors: | Haofei Hong Chen Li Liang Gong Jinfeng Wang Dan Li Jie Shi Zhifang Zhou Zhaohui Huang Zhimeng Wu |
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| Institution: | Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122 China.; Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062 China.; Laboratory of Cancer Epigenetics, School of Medicine, Jiangnan University, Wuxi 214122 China |
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| Abstract: | 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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