journal article·2024-01

Mitigation of Anti‐Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co‐Injection of Nano‐Rapamycin

Ya Chang, Wei Xiong, Chenming Zou, Ping Zeng, Jiazhen Hou, Bahtiyor Muhitdinov, Yuanyuan Shen, Yongzhuo Huang, Shengrong Guo

Small· Volume 20· Issue 3
Publisher page

Abstract

Abstract The induction of anti‐drug antibody (ADA) is a formidable challenge for protein‐based therapy. Trichosanthin (TCS) as a class of ribosome‐inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co‐administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self‐assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co‐injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti‐TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin‐based anticancer therapy and for promoting the clinical translation.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Toxin Mechanisms and Immunotoxins · Monoclonal and Polyclonal Antibodies Research · Transgenic Plants and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

School of Pharmacy Shanghai Jiao Tong University Shanghai 200240 China

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

Artemisinin Research Center Guangzhou University of Chinese Medicine Guangzhou 510450 China

Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences Zhongshan 528437 China

School of Chinese Materia Medica Nanjing University of Chinese Medicine 138 Xianlin Avenue Nanjing 210023 China

Institute of Bioorganic Chemistry Uzbekistan Academy of Sciences Tashkent 100125 Uzbekistan

University of Chinese Academy of Sciences Beijing 100049 China

Funding

National Key Research and Development Program of China · Guangdong Provincial Department of Science and Technology · National Outstanding Youth Science Fund Project of National Natural Science Foundation of China

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