Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementi...Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.展开更多
Objective：To select the specific aptamer of carcinoembryonic antigen （CEA）, one of the most attractive molecule for cancer target therapy and imaging. Methods： Seven rounds in vitro selection were performed agains...Objective：To select the specific aptamer of carcinoembryonic antigen （CEA）, one of the most attractive molecule for cancer target therapy and imaging. Methods： Seven rounds in vitro selection were performed against the purified CEA protein. Ligand-mediated target purification and Co-immunoprecipitation were adopted to verify the specific binding of the aptamer to the purified and native protein separately. Results：The CEA-specific aptamer which can bind both the purified and native protein with the high specificity was obtained. Conclusion：This is the first time the CEA specific apatmer was produced. The results in this study provides the preliminary evidence for further investigation and application of CEA-aptamer in the future.展开更多
BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six...BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six-transmembrane epithelial antigen of the prostate(STEAP) proteins have been recognized and utilized as promising targets for cell-and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.AIM To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.METHODS The expression level of STEAPs in CRC was evaluated using various openresource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immunerelated biomarkers, such as immune infiltration. Immunohistochemical(IHC) experiments were subsequently performed to verify the database conclusions.RESULTS The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However,STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.CONCLUSION Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.展开更多
Globally,hepatocellular carcinoma(HCC)is a leading cause of cancer and cancerrelated deaths.The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low,which results in a ...Globally,hepatocellular carcinoma(HCC)is a leading cause of cancer and cancerrelated deaths.The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low,which results in a poor prognosis.The development of sorafenib for the treatment of HCC has resulted in a new era of molecular targeted therapy for this disease.However,the median overall survival was reported to be barely higher in the sorafenib treatment group than in the control group.Hence,in this review we describe the importance of developing more effective targeted therapies for the management of advanced HCC.Recent investigations of molecular signaling pathways in several cancers have provided some insights into developing molecular therapies that target critical members of these signaling pathways.Proteins involved in the Hedgehog and Notch signaling pathways,Polo-like kinase 1,arginine,histone deacetylases and Glypican-3 can be potential targets in the treatment of HCC.Monotherapy has limited therapeutic efficacy due to the development of inhibitory feedback mechanisms and induction of chemoresistance.Thus,emphasis is now on the development of personalized and combination molecular targeted therapies that can serve as ideal therapeutic strategies for improved management of HCC.展开更多
The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric can...The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.展开更多
Background:Post–cardiac arrest syndrome involves systemic inflammation,which causes subsequent neurological impairments.We investigated the influence of targeted temperature management(TTM)therapy in patients with ou...Background:Post–cardiac arrest syndrome involves systemic inflammation,which causes subsequent neurological impairments.We investigated the influence of targeted temperature management(TTM)therapy in patients with out-of-hospital cardiac arrest(OHCA)after return of spontaneous circulation(ROSC)by observing the changes in circulating CD14^(+)monocytes and the expression of human leukocyte antigen D–related(HLA-DR)and programmed cell death ligand 1(PD-L1)in CD14^(+)monocytes.Methods:Adult patients admitted to the emergency department of Beijing Chao-Yang Hospital after OHCA between January 2017 and March 2018 were included in this study.Thirty control subjects,10 patients with OHCA,and 37 patients with OHCA who received 72 hours of TTM therapy were enrolled.Peripheral blood samples of patients in the OHCA and TTM groups were collected on Days 1 and 3(D1 and D3)after ROSC and evaluated for HLA-DR and PD-L1 expression on CD14^(+)monocytes using flow cytometry.Results:Compared with control subjects,the percentage of circulating CD14^(+)monocytes,HLA-DR+/CD14^(+)monocyte ratios,and mean fluorescence intensity were significantly decreased in patients with OHCA.After ROSC,HLA-DR expression in CD14^(+)monocytes in the TTM group was lower than that in patients with OHCA.However,there were no significant differences in the percentage of PD-L1+/CD14^(+)monocytes or the mean fluorescence intensity between patients with OHCA and healthy volunteers.Conclusion:After ROSC,circulating CD14^(+)monocytes and HLA-DR+/CD14^(+)monocyte ratios decreased significantly in patients with OHCA.Human leukocyte antigen D–related expression in CD14^(+)monocytes was lower in patients treated with TTM.展开更多
基金funded by 2023 Sichuan Scientific and Technological Achievements Transformation Project.Project Number:2023JDZH0024.
文摘Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.
基金This work was supported by the China National Natural Science Foundation(30670958).
文摘Objective：To select the specific aptamer of carcinoembryonic antigen （CEA）, one of the most attractive molecule for cancer target therapy and imaging. Methods： Seven rounds in vitro selection were performed against the purified CEA protein. Ligand-mediated target purification and Co-immunoprecipitation were adopted to verify the specific binding of the aptamer to the purified and native protein separately. Results：The CEA-specific aptamer which can bind both the purified and native protein with the high specificity was obtained. Conclusion：This is the first time the CEA specific apatmer was produced. The results in this study provides the preliminary evidence for further investigation and application of CEA-aptamer in the future.
基金Supported by the National Natural Science Foundation of China,No. 81501539the Natural Science Foundation of Guangdong Province,No. 2021A1515012180 and 2016A030312008+2 种基金the Special Grant for Key Area Programs of Guangdong Department of Education,No. 2021ZDZX2004the Science and Technology Special Project of Guangdong Province,No. 210715216902829“Dengfeng Project” for the Construction of High-level Hospitals in Guangdong Province-First Affiliated Hospital of Shantou University College Supporting Funding,No. 202003-10。
文摘BACKGROUND Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers(CRC). Human six-transmembrane epithelial antigen of the prostate(STEAP) proteins have been recognized and utilized as promising targets for cell-and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated.AIM To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas.METHODS The expression level of STEAPs in CRC was evaluated using various openresource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immunerelated biomarkers, such as immune infiltration. Immunohistochemical(IHC) experiments were subsequently performed to verify the database conclusions.RESULTS The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However,STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees.CONCLUSION Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.
文摘Globally,hepatocellular carcinoma(HCC)is a leading cause of cancer and cancerrelated deaths.The therapeutic efficacy of locoregional and systemic treatment in patients with advanced HCC remains low,which results in a poor prognosis.The development of sorafenib for the treatment of HCC has resulted in a new era of molecular targeted therapy for this disease.However,the median overall survival was reported to be barely higher in the sorafenib treatment group than in the control group.Hence,in this review we describe the importance of developing more effective targeted therapies for the management of advanced HCC.Recent investigations of molecular signaling pathways in several cancers have provided some insights into developing molecular therapies that target critical members of these signaling pathways.Proteins involved in the Hedgehog and Notch signaling pathways,Polo-like kinase 1,arginine,histone deacetylases and Glypican-3 can be potential targets in the treatment of HCC.Monotherapy has limited therapeutic efficacy due to the development of inhibitory feedback mechanisms and induction of chemoresistance.Thus,emphasis is now on the development of personalized and combination molecular targeted therapies that can serve as ideal therapeutic strategies for improved management of HCC.
文摘The treatment of gastrointestinal cancer has always been a crucial research area,and targeted therapy has been receiving increasing attention.At present,the effect of targeted therapy is unsatisfactory for gastric cancer.Thus,the discovery of new targets is crucial.Claudin 18.2(CLDN18.2),a member of the claudin family,belongs to the tight junction protein family that controls the flow of molecules between cell layers.CLDN18.2 expression has been discussed in many studies.In recent years,there have been many studies on targeted therapy with CLDN18.2-ideal monoclonal antibody 362.Furthermore,CLDN18.2-specific chimeric antigen receptor T therapy has been used for CLDN18.2-positive tumors,such as gastric and pancreatic cancers.Considerable research has been focused on CLDN18.2.CLDN18.2,a newly discovered marker for precise targeted therapy of gastric cancer,could offer new hope for the treatment of gastric cancer.
基金the National Natural Science Foundation of China(Grant No.81372025).
文摘Background:Post–cardiac arrest syndrome involves systemic inflammation,which causes subsequent neurological impairments.We investigated the influence of targeted temperature management(TTM)therapy in patients with out-of-hospital cardiac arrest(OHCA)after return of spontaneous circulation(ROSC)by observing the changes in circulating CD14^(+)monocytes and the expression of human leukocyte antigen D–related(HLA-DR)and programmed cell death ligand 1(PD-L1)in CD14^(+)monocytes.Methods:Adult patients admitted to the emergency department of Beijing Chao-Yang Hospital after OHCA between January 2017 and March 2018 were included in this study.Thirty control subjects,10 patients with OHCA,and 37 patients with OHCA who received 72 hours of TTM therapy were enrolled.Peripheral blood samples of patients in the OHCA and TTM groups were collected on Days 1 and 3(D1 and D3)after ROSC and evaluated for HLA-DR and PD-L1 expression on CD14^(+)monocytes using flow cytometry.Results:Compared with control subjects,the percentage of circulating CD14^(+)monocytes,HLA-DR+/CD14^(+)monocyte ratios,and mean fluorescence intensity were significantly decreased in patients with OHCA.After ROSC,HLA-DR expression in CD14^(+)monocytes in the TTM group was lower than that in patients with OHCA.However,there were no significant differences in the percentage of PD-L1+/CD14^(+)monocytes or the mean fluorescence intensity between patients with OHCA and healthy volunteers.Conclusion:After ROSC,circulating CD14^(+)monocytes and HLA-DR+/CD14^(+)monocyte ratios decreased significantly in patients with OHCA.Human leukocyte antigen D–related expression in CD14^(+)monocytes was lower in patients treated with TTM.
