Universal endogenous antibody recruiting nanobodies capable of triggering immune effectors for targeted cancer immunotherapy
Open Access
- 11 February 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Chemical Science
- Vol. 12 (12), 4623-4630
- https://doi.org/10.1039/d0sc05332e
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).Keywords
Funding Information
- National Natural Science Foundation of China (21472070, 32000904, 21602084, 21907038)
- Natural Science Foundation of Jiangsu Province (BK20200601)
- National Postdoctoral Program for Innovative Talents (BX20200153)
- China Postdoctoral Science Foundation (2018M632227)
- Higher Education Discipline Innovation Project (111-2-06)
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