Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed ...Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed the whitening efficacy of various concentrations of immune cells and stem cell conditioned media. The author tried to study a conditioned medium that has a strong whitening effect even with a composition of less than 20% (the most used concentration in cosmetics). Because of the fact that the conditioned medium contains various cytokines and growth factors secreted by stem cells or immune cells, it is known to have effects such as wound healing, antioxidant, and whitening effect. Recently, stem cells have been used not only in the development of cosmetic raw materials but also in skincare procedures, and there are reports being released of cosmetics using immune cells conditioned medium. The concentration-dependent whitening effect equivalently increased as the concentration of the mono-cultured conditioned medium was obtained through the stem cells or immune cells culture. In the case of co-culture, whitening results are like the effect of positive control such as arbutin in the medium carrying only 10% of the co-cultured conditioned medium. It is possible that enhanced whitening efficiency in co-cultured conditioned medium leads to a major innovation in the global cosmetic market.展开更多
Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung c...Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer progression.The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments.Therefore,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing effect.In summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.展开更多
Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly...Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly used to treat hematological malignancies,CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety,reduced risk of graft-versus-host disease,fewer side effects,and amplified antitumor efficacy.Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models.We brought forth herein the design principle of CAR-NK cells,highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells,briefly delved into discussed major roadblocks in CAR-NK therapy,and discussed potential solutions to surmount these challenges.Given the accelerated progress in both basic and translational studies on immune cell engineering,CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.展开更多
Alcoholic liver disease(ALD)represents a wide spectrum of disease from simple steatosis to cirrhosis.Although there have been multiple attempts to treat ALD,its treatment is still based on abstinence from alcohol and ...Alcoholic liver disease(ALD)represents a wide spectrum of disease from simple steatosis to cirrhosis.Although there have been multiple attempts to treat ALD,its treatment is still based on abstinence from alcohol and using corticosteroids in specified cases.However,nearly 40%of patients with ALD who are in need of treatment are unresponsive to the current treatments,which implies a new paradigm shift for the treatment of ALD.Traditionally,earlier studies have focused on the abnormal metabolism occurring in the hepatocytes as a protagonist in the pathogenesis of ALD.However,increasing evidence suggests that non-parenchymal cells,such as hepatic stellate cells(HSCs),Kupffer cells,liver sinusoidal endothelial cells,and immune cells around the hepatocytes have critical roles in multiple stages of ALD either by direct or indirect cell-to-cell interactions.For instance,in the early stage of ALD,Kupffer cells and HSCs located closely to hepatocytes contribute to the development of alcoholic steatosis and inflammation through the secretion of various inflammatory cytokines(immunologic pathways)and the activation of the endocannabinoid system(metabolic pathways).While the stage of ALD progresses to alcoholic hepatitis and fibrosis,various cell-to-cell interactions with infiltrating immune cells become highly significant at the multicellular level.This review explains the diverse roles of non-parenchymal cells in the progression of ALD,as well as potential therapeutic strategies to treat ALD.展开更多
The RNA helicase DHX15 is widely expressed in immune cells and traditionally thought to be an RNA splicing factor or a viral RNA sensor.However,the role of DHX15 in NK-cell activities has not been studied thus far.Her...The RNA helicase DHX15 is widely expressed in immune cells and traditionally thought to be an RNA splicing factor or a viral RNA sensor.However,the role of DHX15 in NK-cell activities has not been studied thus far.Here,we generated Dhx15-floxed mice and found that conditional deletion of Dhx15 in NK cells(Ncr1CreDhx15fl/fl mice)resulted in a marked reduction in NK cells in the periphery and that the remaining Dhx15-deleted NK cells failed to acquire a mature phenotype.As a result,Dhx15-deleted NK cells exhibited profound defects in their cytolytic functions.We also found that deletion of Dhx15 in NK cells abrogated their responsiveness to IL-15,which was associated with inhibition of IL-2/IL-15Rβ(CD122)expression and IL-15R signaling.The defects in Dhx15-deleted NK cells were rescued by ectopic expression of a constitutively active form of STAT5.Mechanistically,DHX15 did not affect CD122 mRNA splicing and stability in NK cells but instead facilitated the surface expression of CD122,likely through interaction with its 3′UTR,which was dependent on the ATPase domain of DHX15 rather than its splicing domain.Collectively,our data identify a key role for DHX15 in regulating NK-cell activities and provide novel mechanistic insights into how DHX15 regulates the IL-15 signaling pathway in NK cells.展开更多
Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and cancer.However,NK cell therapies are limited by the fact that target cells evade NK cells,...Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and cancer.However,NK cell therapies are limited by the fact that target cells evade NK cells,for example,in latent reservoirs(in HIV)or through upregulation of inhibitory signals(in cancer).To address this limitation,we describe a biodegradable nanoparticlebased“priming”approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells.We present poly(lactic-co-glycolic acid)(PLGA)nanodepots(NDs)that co-encapsulate prostratin,a latency-reversing agent,and anti-CD25(aCD25),a cell surface binding antibody,to enhance primary NK cell function against HIV and cancer.We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs(termed Pro-aCD25-NDs).Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs.The NDs successfully released both active prostratin and anti-CD25,and with controllable release kinetics.When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells,the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25,and other controls.These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.展开更多
The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunothera...The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention.Variable region-retaining antibody fragments,such as antigen-binding fragment(Fab),single-chain variable fragment(scFv),bispecific antibody,and bi/trispecific cell engagers,are engineered with humanization,multivalent antibody construction,affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency,efficacy and specificity.In this review,we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.展开更多
文摘Many researchers have described that mesenchymal stem cells conditioned medium and immune cells conditioned medium have a clear whitening effect when they are used as cosmetic ingredients. In this study, we confirmed the whitening efficacy of various concentrations of immune cells and stem cell conditioned media. The author tried to study a conditioned medium that has a strong whitening effect even with a composition of less than 20% (the most used concentration in cosmetics). Because of the fact that the conditioned medium contains various cytokines and growth factors secreted by stem cells or immune cells, it is known to have effects such as wound healing, antioxidant, and whitening effect. Recently, stem cells have been used not only in the development of cosmetic raw materials but also in skincare procedures, and there are reports being released of cosmetics using immune cells conditioned medium. The concentration-dependent whitening effect equivalently increased as the concentration of the mono-cultured conditioned medium was obtained through the stem cells or immune cells culture. In the case of co-culture, whitening results are like the effect of positive control such as arbutin in the medium carrying only 10% of the co-cultured conditioned medium. It is possible that enhanced whitening efficiency in co-cultured conditioned medium leads to a major innovation in the global cosmetic market.
基金supported by the National Natural Science Fund for Distinguished Young Scholars(No.82225025)the National Natural Science Foundation of China(Nos.21877049,32171296)+1 种基金China Postdoctoral Science Foundation(No.2021M690066)Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110300).
文摘Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer progression.The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments.Therefore,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing effect.In summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.
基金Cancer Prevention and Research Institute of Texas(Grant/Award Number:RP210070)National Cancer Institute(Grant/Award Number:R01CA232017)Welch Foundation(Grant/Award Number:BE-1913-20220331)。
文摘Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly used to treat hematological malignancies,CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety,reduced risk of graft-versus-host disease,fewer side effects,and amplified antitumor efficacy.Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models.We brought forth herein the design principle of CAR-NK cells,highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells,briefly delved into discussed major roadblocks in CAR-NK therapy,and discussed potential solutions to surmount these challenges.Given the accelerated progress in both basic and translational studies on immune cell engineering,CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.
基金This work was supported by the National Research Foundation of Korea(NRF)grant(2018R1A2A1A05077608)the Korea Mouse Phenotyping Project(2014M3A9D5A01073556)the Intelligent Synthetic Biology Center of Global Frontier Project(2011-0031955)funded by the Korea government(MSIT).
文摘Alcoholic liver disease(ALD)represents a wide spectrum of disease from simple steatosis to cirrhosis.Although there have been multiple attempts to treat ALD,its treatment is still based on abstinence from alcohol and using corticosteroids in specified cases.However,nearly 40%of patients with ALD who are in need of treatment are unresponsive to the current treatments,which implies a new paradigm shift for the treatment of ALD.Traditionally,earlier studies have focused on the abnormal metabolism occurring in the hepatocytes as a protagonist in the pathogenesis of ALD.However,increasing evidence suggests that non-parenchymal cells,such as hepatic stellate cells(HSCs),Kupffer cells,liver sinusoidal endothelial cells,and immune cells around the hepatocytes have critical roles in multiple stages of ALD either by direct or indirect cell-to-cell interactions.For instance,in the early stage of ALD,Kupffer cells and HSCs located closely to hepatocytes contribute to the development of alcoholic steatosis and inflammation through the secretion of various inflammatory cytokines(immunologic pathways)and the activation of the endocannabinoid system(metabolic pathways).While the stage of ALD progresses to alcoholic hepatitis and fibrosis,various cell-to-cell interactions with infiltrating immune cells become highly significant at the multicellular level.This review explains the diverse roles of non-parenchymal cells in the progression of ALD,as well as potential therapeutic strategies to treat ALD.
基金This project was supported by National Institutes of Health grants(R01AI080779 and R01 A1155488).
文摘The RNA helicase DHX15 is widely expressed in immune cells and traditionally thought to be an RNA splicing factor or a viral RNA sensor.However,the role of DHX15 in NK-cell activities has not been studied thus far.Here,we generated Dhx15-floxed mice and found that conditional deletion of Dhx15 in NK cells(Ncr1CreDhx15fl/fl mice)resulted in a marked reduction in NK cells in the periphery and that the remaining Dhx15-deleted NK cells failed to acquire a mature phenotype.As a result,Dhx15-deleted NK cells exhibited profound defects in their cytolytic functions.We also found that deletion of Dhx15 in NK cells abrogated their responsiveness to IL-15,which was associated with inhibition of IL-2/IL-15Rβ(CD122)expression and IL-15R signaling.The defects in Dhx15-deleted NK cells were rescued by ectopic expression of a constitutively active form of STAT5.Mechanistically,DHX15 did not affect CD122 mRNA splicing and stability in NK cells but instead facilitated the surface expression of CD122,likely through interaction with its 3′UTR,which was dependent on the ATPase domain of DHX15 rather than its splicing domain.Collectively,our data identify a key role for DHX15 in regulating NK-cell activities and provide novel mechanistic insights into how DHX15 regulates the IL-15 signaling pathway in NK cells.
基金Research reported in this publication was supported in part by the George Washington Cancer Center and by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R21AI136102The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
文摘Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and cancer.However,NK cell therapies are limited by the fact that target cells evade NK cells,for example,in latent reservoirs(in HIV)or through upregulation of inhibitory signals(in cancer).To address this limitation,we describe a biodegradable nanoparticlebased“priming”approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells.We present poly(lactic-co-glycolic acid)(PLGA)nanodepots(NDs)that co-encapsulate prostratin,a latency-reversing agent,and anti-CD25(aCD25),a cell surface binding antibody,to enhance primary NK cell function against HIV and cancer.We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs(termed Pro-aCD25-NDs).Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs.The NDs successfully released both active prostratin and anti-CD25,and with controllable release kinetics.When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells,the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25,and other controls.These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-017。
文摘The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention.Variable region-retaining antibody fragments,such as antigen-binding fragment(Fab),single-chain variable fragment(scFv),bispecific antibody,and bi/trispecific cell engagers,are engineered with humanization,multivalent antibody construction,affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency,efficacy and specificity.In this review,we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.