Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient prol...Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.展开更多
A high oleic acid rapeseed material MI5 (derived from Xiangyou 15 variety) has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with X...A high oleic acid rapeseed material MI5 (derived from Xiangyou 15 variety) has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with Xiangyou 15 variety. To find out the difference between high oleic acid rapeseed material and Xiangyou 15 seedling, a comparative proteomic approach based on 2-DE and mass spectrometry was adopted. A total of 277 protein spots showed a significant change in intensity by more than 2.0-fold from M15 compared with Xiangyou 15 variety. Among them, 48 spots that changed at least 3.0-fold were excised from gels and successfully identified by MALDI-TOF/TOF MS. The identified proteins involved in metabolism of carbohydrate and energy (75%), stress and defense (8.3%), photosynthesis (6.3%), protein metabolism (2.1%) and other functions (8.3%). Then real-time quantitative PCR (qPCR) analysis was used to verify the expression levels of differentially expressed proteins, but the results did well agree with the proteomic results. In this work, most of the proteins involved in metabolism of carbohydrate and energy have higher expression in M15, which may reveal M15 has higher metabolism ability. These results provided much information to understand the differences between high oleic acid rapeseed material and Xiangyou 15 variety, which will be useful to screen high oleic rapeseed materials in seedling period.展开更多
基金supported by the National Natural Science Foundation of China(Nos.52025035,51873206 and 52203198)the Project of Health research talents Project of Jilin Province(No.2020SCZ06)+1 种基金the Project of Jilin Province Development and Reform Commission(No.2021C043-6)the Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(No.20210504001GH).
文摘Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy.
基金Acknowledgements This work was financially supported by the Natural Science Foundation of China (31201240, 31000722, 31200522), National High Technology Research and Development Program of China (2012AA101107-3), the foundation of Key Laboratory of Biology and Genetic Improvement of Oil Crops (2014008), and the crop science foundation of Hunan Agricultural University (ZWKF201302).
文摘A high oleic acid rapeseed material MI5 (derived from Xiangyou 15 variety) has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with Xiangyou 15 variety. To find out the difference between high oleic acid rapeseed material and Xiangyou 15 seedling, a comparative proteomic approach based on 2-DE and mass spectrometry was adopted. A total of 277 protein spots showed a significant change in intensity by more than 2.0-fold from M15 compared with Xiangyou 15 variety. Among them, 48 spots that changed at least 3.0-fold were excised from gels and successfully identified by MALDI-TOF/TOF MS. The identified proteins involved in metabolism of carbohydrate and energy (75%), stress and defense (8.3%), photosynthesis (6.3%), protein metabolism (2.1%) and other functions (8.3%). Then real-time quantitative PCR (qPCR) analysis was used to verify the expression levels of differentially expressed proteins, but the results did well agree with the proteomic results. In this work, most of the proteins involved in metabolism of carbohydrate and energy have higher expression in M15, which may reveal M15 has higher metabolism ability. These results provided much information to understand the differences between high oleic acid rapeseed material and Xiangyou 15 variety, which will be useful to screen high oleic rapeseed materials in seedling period.