Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale productio...Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.展开更多
Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates o...Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.展开更多
基金supported by the National Natural Science Foundation of China (81071850 and 81301307)
文摘Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.
文摘Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.
