Mannosylated engineered trichosanthin-legumain protein vaccine hydrogel for breast cancer immunotherapy.

Autor: Chen G; Artemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510450, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Zhongshan Institute for Drug Discovery, The Institutes of Drug Discovery and Development, CAS, Zhongshan 528437, China., Xiong W; Artemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510450, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Zhongshan Institute for Drug Discovery, The Institutes of Drug Discovery and Development, CAS, Zhongshan 528437, China., Gu Z; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau SAR, China., Gao Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China., Hou J; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, 10, Nanjing 210023, China., Long L; Artemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510450, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Zhongshan Institute for Drug Discovery, The Institutes of Drug Discovery and Development, CAS, Zhongshan 528437, China., Wang H; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China., Asrorov AM; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, 83, M. Ulughbek Street, Tashkent 100125, Uzbekistan., Muhitdinov B; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, 83, M. Ulughbek Street, Tashkent 100125, Uzbekistan., Xu Q; Artemisinin Research Center, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou 510450, China. Electronic address: xuqin@gzucm.edu.cn., Huang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China; Zhongshan Institute for Drug Discovery, The Institutes of Drug Discovery and Development, CAS, Zhongshan 528437, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, 10, Nanjing 210023, China. Electronic address: yzhuang@simm.ac.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2022 Dec 31; Vol. 223 (Pt A), pp. 1485-1494. Date of Electronic Publication: 2022 Nov 14.
DOI: 10.1016/j.ijbiomac.2022.11.045
Abstrakt: The development of cancer vaccines based on tumor-associated antigens is hurdled by lack of an efficient adjuvant and insufficient efficacy. To improve the efficacy of vaccines, a genetically-engineered method was employed in this work to achieve the codelivery of antigen and adjuvant to enhance immune responses. Trichosanthin is a plant-derived protein that possesses cancer immune stimulation function. A genetically engineered protein vaccine composed of trichosanthin (adjuvant) and legumain domain (a peptidic antigen) was constructed, which was further chemically modified with mannose for targeting dendritic cells (DCs). The method is facile and ready for scaling up for massive production. Such a "two-in-one" vaccine is advantageous for codelivery for augmenting the immune responses. The vaccine inhibited the tumors by triggering a robust cytotoxic T lymphocyte response in the orthotopic-breast-tumor mice. Furthermore, the vaccine was loaded into the temperature-sensitive hydrogel based on Pluronic F127 for implanting use in the post-surgical site. The sustained-released vaccine from the hydrogel inhibited not only the tumor recurrence but also the lung metastases of breast cancer. These findings demonstrated that it was a safe and effective vaccination for breast cancer immunotherapy in a prophylactical and therapeutical manner for remodeling the tumor immune microenvironment and arresting tumor growth.
Competing Interests: Declaration of competing interest All authors claim there are no financial or personal relationships that may be perceived as influencing this work.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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