The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes(LNs) drainage of antig...The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes(LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin(SV) adjuvant loaded Au nanocages(AuNCs)as cores(AuNCs/SV) and folic acid modified thermal-sensitive liposomes(FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy(PTT) induced the release of tumor-derived protein antigens(TDPAs) and the shedding of FATSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine(AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.展开更多
目的:探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗难治性类风湿关节炎的临床疗效。方法:50例难治性类风湿关节炎(refractory or resistant rheumatoid arthritis,RRA)随机分为治疗组25例和对照组25例。治疗组:益赛普25...目的:探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗难治性类风湿关节炎的临床疗效。方法:50例难治性类风湿关节炎(refractory or resistant rheumatoid arthritis,RRA)随机分为治疗组25例和对照组25例。治疗组:益赛普25mg,皮下注射,每周2次,疗程6个月;对照组:安慰剂25mg,皮下注射,每周2次,疗程24周。疗效评价采用美国风湿病学会(ACR)疗效评定标准。结果:治疗组ACR20、ACR50、ACR70有效率均高于对照组(P<0.05),治疗组24周ACR20、ACR50、ACR70的有效率高于治疗组4周(P<0.05);治疗组发生不良事件6例(24.0%)高于对照组3例(12.0%)。结沦:rhTNFR:Fc治疗难治性类风湿关节炎有较好的疗效。展开更多
Objective:To develop an agent that is more active against receptor bearing target cells without increasing the toxic effect on non target cells.Methods:By the use of molecular biology techniques,we designed and constr...Objective:To develop an agent that is more active against receptor bearing target cells without increasing the toxic effect on non target cells.Methods:By the use of molecular biology techniques,we designed and constructed a fusion protein 5′IL6 TNF △ by connecting the human interleukin 6 (hIL 6) gene and a human tumor necrosis factor α derivative (TNF △) gene through a synthetic linker sequence followed by subsequent expression in E.coli .Results:In cytotoxicity assay with myeloma cell line U266,the normal type of 5′IL6 TNF △ showed an antitumor activity 3 times higher than that of TNF △;and the antitumor activity of 5′IL6 TNF △ blocked by IL 6R was only 1/30 of that of normal type of 5′IL6 TNF △.Meanwhile,the 5′IL6 TNF △ blocked by anti TNF antibody did not show any cytotoxicity to U266 cells.In activity assay with L929 cells,the toxic effect of the fusion protein was found 1/22 of that of TNF △.Conclusion:The 5′IL6 TNF △ fusion protein might be a useful cytotoxic agent in cancer treatment.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant Nos.U1804183,81901878 and 81874304)China Postdoctoral Science Foundation (2019M662553,China)Key Scientific Research Project (Education Department of Henan Province,20HASTIT049,China)。
文摘The continuing challenges that limit effectiveness of tumor therapeutic vaccines were high heterogeneity of tumor immunogenicity, low bioactivity of antigens, as well as insufficient lymph nodes(LNs) drainage of antigens and adjuvants. Transportation of in situ neoantigens and adjuvants to LNs may be an effective approach to solve the abovementioned problems. Therefore, an FA-TSL/AuNCs/SV nanoplatform was constructed by integrating simvastatin(SV) adjuvant loaded Au nanocages(AuNCs)as cores(AuNCs/SV) and folic acid modified thermal-sensitive liposomes(FA-TSL) as shells to enhance de novo antitumor immunity. After accumulation in tumor guided by FA, AuNCs mediated photothermal therapy(PTT) induced the release of tumor-derived protein antigens(TDPAs) and the shedding of FATSL. Exposed AuNCs/SV soon captured TDPAs to form in situ recombinant vaccine(AuNCs/SV/TDPAs). Subsequently, AuNCs/SV/TDPAs could efficiently transport to draining LNs owing to the hyperthermia induced vasodilation effect and small particle size, achieving co-delivery of antigens and adjuvant for initiation of specific T cell response. In melanoma bearing mice, FA-TSL/AuNCs/SV and laser irradiation effectively ablated primary tumor, against metastatic tumors and induced immunological memory. This approach served a hyperthermia enhanced platform drainage to enable robust personalized cancer vaccination.
文摘目的:探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)治疗难治性类风湿关节炎的临床疗效。方法:50例难治性类风湿关节炎(refractory or resistant rheumatoid arthritis,RRA)随机分为治疗组25例和对照组25例。治疗组:益赛普25mg,皮下注射,每周2次,疗程6个月;对照组:安慰剂25mg,皮下注射,每周2次,疗程24周。疗效评价采用美国风湿病学会(ACR)疗效评定标准。结果:治疗组ACR20、ACR50、ACR70有效率均高于对照组(P<0.05),治疗组24周ACR20、ACR50、ACR70的有效率高于治疗组4周(P<0.05);治疗组发生不良事件6例(24.0%)高于对照组3例(12.0%)。结沦:rhTNFR:Fc治疗难治性类风湿关节炎有较好的疗效。
文摘Objective:To develop an agent that is more active against receptor bearing target cells without increasing the toxic effect on non target cells.Methods:By the use of molecular biology techniques,we designed and constructed a fusion protein 5′IL6 TNF △ by connecting the human interleukin 6 (hIL 6) gene and a human tumor necrosis factor α derivative (TNF △) gene through a synthetic linker sequence followed by subsequent expression in E.coli .Results:In cytotoxicity assay with myeloma cell line U266,the normal type of 5′IL6 TNF △ showed an antitumor activity 3 times higher than that of TNF △;and the antitumor activity of 5′IL6 TNF △ blocked by IL 6R was only 1/30 of that of normal type of 5′IL6 TNF △.Meanwhile,the 5′IL6 TNF △ blocked by anti TNF antibody did not show any cytotoxicity to U266 cells.In activity assay with L929 cells,the toxic effect of the fusion protein was found 1/22 of that of TNF △.Conclusion:The 5′IL6 TNF △ fusion protein might be a useful cytotoxic agent in cancer treatment.
