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One-month zero-order sustained release and tumor eradication after a single subcutaneous injection of interferon alpha fused with a body-temperature-responsive polypeptide

Author:
Wang, Zhuoran, Guo, Jianwen, Ning, Jing, Feng, Xiaoyu, Liu, Xinyu, Sun, Jiawei, Chen, Xiangmei, Lu, Fengmin, Gao, Weiping
Source:
Biomaterials science 2018 v.7 no.1 pp. 104-112
ISSN:
2047-4849
Subject:
adverse effects, animal models, antibodies, biopharmaceuticals, biosafety, half life, humans, neoplasms, patient compliance, polypeptides, subcutaneous injection, therapeutics
Abstract:
Most therapeutic proteins except antibodies necessitate frequent dosing at high concentrations due to their short circulation half-lives, leading to limited therapeutic efficacy, serious adverse side effects and poor patient compliance. Herein we report a strategy of thermoresponsive polypeptide fusion to genetically engineer a super-long-acting interferon alpha fused with a body-temperature-responsive polypeptide. After a single subcutaneous injection in a mouse model, this interferon alpha can in situ form a depot to show a one-month zero-order sustained release, which would enable a once-trimonthly dosing in humans. As a result, it exhibits greatly enhanced tumor accumulation and tumor eradication as well as substantially improved tolerability and biosafety. This strategy provides a promising solution to dramatically enhance the pharmacological performance of therapeutic proteins with short circulation half-lives while reducing the side effects.
Agid:
6262276