In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PE...In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 NPs.PEG-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity,immunogenic cell death(ICD)induction ability and anti-tumor efficacy.Dynamic light scattering(DLS)results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 nm.In vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner,and it induced the ICD of B16-F10 cells.In vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor tissues.Moreover,it increased the rate of CD8+T cells in the spleen.In summary,PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs,which was a safe and effective combined delivery system.展开更多
Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biolog...Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.展开更多
基金The National Natural Science Foundation of China(Grants No.31671017,81872809)the National Key Research and Development Program of China(Grants No.2017YFA0205600)Beijing Natural Science Foundation(Grants No.7162108)。
文摘In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 NPs.PEG-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity,immunogenic cell death(ICD)induction ability and anti-tumor efficacy.Dynamic light scattering(DLS)results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 nm.In vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner,and it induced the ICD of B16-F10 cells.In vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor tissues.Moreover,it increased the rate of CD8+T cells in the spleen.In summary,PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs,which was a safe and effective combined delivery system.
文摘Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.
