T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T...T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.展开更多
In an attempt to improve upon the end results obtained in treating colorectal cancer it was apparent that the earlier the diagnosis that could be obtained, the better the chance for obtaining desired results. In the c...In an attempt to improve upon the end results obtained in treating colorectal cancer it was apparent that the earlier the diagnosis that could be obtained, the better the chance for obtaining desired results. In the case of more advanced tumors typified by later stage colorectal cancer, surgical debulking is an important part of the treatment strategy. Here the use of additional therapeu-tic modalities including chemotherapy and present day immunotherapy has failed to accomplish the desired im-provements that have been sought after. Adjuvant ther-apy, has offered little to the overall survival. The concept of early detection is now recognized as the initial step in reaching proper end results and can readily be demon-strated from colorectal cancer studies. Here survival has been found to be a reflection of the stage at which the tumor is first identified and treated. When specific mono-clonals targeting colorectal cancer are employed diagnos-tically, we have been able to demonstrate detection of colorectal cancer at its inception as a premalignant lesion, such that genotypic features can be identified before the phenotypic appearance of cancer can be noted.展开更多
Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis...Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.展开更多
T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of...T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.展开更多
The tumor microenvironment(TME)is composed of different cellular and non-cellular elements.Constant inter-actions between tumor cells and the TME are responsible for tumor initiation,tumor progression,and responses to...The tumor microenvironment(TME)is composed of different cellular and non-cellular elements.Constant inter-actions between tumor cells and the TME are responsible for tumor initiation,tumor progression,and responses to therapies.Immune cells in the TME can be classified into two broad categories,namely adaptive and innate immunity.Targeting these immune cells has attracted substantial research and clinical interest.Current research focuses on identifying key molecular players and developing targeted therapies.These approaches may offer more efficient ways of treating different cancers.In this review,we explore the heterogeneity of the TME in non-small cell lung cancer,summarize progress made in targeting the TME in preclinical and clinical studies,discuss the potential predictive value of the TME in immunotherapy,and highlight the promising effects of bispecific antibodies in the era of immunotherapy.展开更多
INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SL...INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .展开更多
目的:通过双重免疫荧光染色法鉴定不同肺组织内是否存在Clara细胞特异性抗原(Clara cell specific antigen,CCA)和肺泡表面活性蛋白C(surfactant protein C,SP-C)共表达的双阳性细胞(double positive cell,DPCs)CCA+SP-C+细胞,为后续开...目的:通过双重免疫荧光染色法鉴定不同肺组织内是否存在Clara细胞特异性抗原(Clara cell specific antigen,CCA)和肺泡表面活性蛋白C(surfactant protein C,SP-C)共表达的双阳性细胞(double positive cell,DPCs)CCA+SP-C+细胞,为后续开展肺干细胞的相关研究提供实验基础。方法:取成年鼠(小鼠、大鼠)和新生鼠(小鼠、大鼠)的正常肺组织,人的肺鳞癌、腺癌的癌组织和癌旁组织,冰冻切片,进行双重免疫荧光染色,通过激光扫描共聚焦显微镜观察肺组织内是否存在DPCs。每例标本观察时镜下随机选择4~6个视野,计数100~200个肺细胞,得出每百个细胞内DPCs百分率,采用SPSS 11.0统计软件包对数据进行分析。结果:在成年鼠和新生鼠的正常肺组织中均发现了DPCs的存在,在人的肺腺癌组织中也发现了DPCs,而在鳞癌组织中未见DPCs;在人的癌旁组织DPCs数量明显多于相对应的癌组织(P<0.05)。结论:本研究不仅证实了DPCs细胞存在的广泛性,而且在人的肺腺癌组织中发现了DPCs,同时发现癌旁组织内的DPCs明显多于癌组织,为后续进一步分离、纯化DPCs,研究正常肺干细胞和肺癌干细胞的生物学特性提供了实验基础。展开更多
Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has b...Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.展开更多
基金supported by the National Natural Science Foundation of China(Nos.32070940 and 81991491)the China Postdoctoral Science Foundation(No.2021M700115)+2 种基金the Postdoctoral Innovation Talents Support Program(No.BX20220189,China)the Science and Technology Planning Project of Fujian Province(No.2022L3080,China)the CAMS Innovation Fund for Medical Sciences(No.2019RU022,China).
文摘T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.
文摘In an attempt to improve upon the end results obtained in treating colorectal cancer it was apparent that the earlier the diagnosis that could be obtained, the better the chance for obtaining desired results. In the case of more advanced tumors typified by later stage colorectal cancer, surgical debulking is an important part of the treatment strategy. Here the use of additional therapeu-tic modalities including chemotherapy and present day immunotherapy has failed to accomplish the desired im-provements that have been sought after. Adjuvant ther-apy, has offered little to the overall survival. The concept of early detection is now recognized as the initial step in reaching proper end results and can readily be demon-strated from colorectal cancer studies. Here survival has been found to be a reflection of the stage at which the tumor is first identified and treated. When specific mono-clonals targeting colorectal cancer are employed diagnos-tically, we have been able to demonstrate detection of colorectal cancer at its inception as a premalignant lesion, such that genotypic features can be identified before the phenotypic appearance of cancer can be noted.
文摘Follicular lymphoma(FL)is the most common low-grade lymphoma,and although nodal FL is highly responsive to treatment,the majority of patients relapse repeatedly,and the disease has been incurable with a poor prognosis.However,primary FL of the gastrointestinal tract has been increasingly detected in Japan,especially due to recent advances in small bowel endoscopy and increased opportunities for endoscopic examinations and endoscopic diagnosis.However,many cases are detected at an early stage,and the prognosis is good in many cases.In contrast,in Europe and the United States,gastrointestinal FL has long been considered to be present in 12%-24%of Stage-IV patients,and the number of advanced gastrointestinal cases is expected to increase.This editorial provides an overview of the recent therapeutic advances in nodal FL,including antibody-targeted therapy,bispecific antibody therapy,epigenetic modulation,and chimeric antigen receptor T-cell therapy,and reviews the latest therapeutic manuscripts published in the past year.Based on an understanding of the therapeutic advances in nodal FL,we also discuss future possibilities for gastroenterologists to treat gastrointestinal FL,especially in advanced cases.
基金This work was supported by the National Natural Science Foundation of China(Nos.81773621 and 82073751)the National Science and Technology Major Project(No.2019ZX09201001,China).
文摘T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.
基金This study was conducted with support from the National Natural Science Foundation of China(No.82073147 to Q.J.)supported by Foundation from Third Military Medical University(TMMU)(No.2018XLC1008).
文摘The tumor microenvironment(TME)is composed of different cellular and non-cellular elements.Constant inter-actions between tumor cells and the TME are responsible for tumor initiation,tumor progression,and responses to therapies.Immune cells in the TME can be classified into two broad categories,namely adaptive and innate immunity.Targeting these immune cells has attracted substantial research and clinical interest.Current research focuses on identifying key molecular players and developing targeted therapies.These approaches may offer more efficient ways of treating different cancers.In this review,we explore the heterogeneity of the TME in non-small cell lung cancer,summarize progress made in targeting the TME in preclinical and clinical studies,discuss the potential predictive value of the TME in immunotherapy,and highlight the promising effects of bispecific antibodies in the era of immunotherapy.
文摘INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .
文摘目的:通过双重免疫荧光染色法鉴定不同肺组织内是否存在Clara细胞特异性抗原(Clara cell specific antigen,CCA)和肺泡表面活性蛋白C(surfactant protein C,SP-C)共表达的双阳性细胞(double positive cell,DPCs)CCA+SP-C+细胞,为后续开展肺干细胞的相关研究提供实验基础。方法:取成年鼠(小鼠、大鼠)和新生鼠(小鼠、大鼠)的正常肺组织,人的肺鳞癌、腺癌的癌组织和癌旁组织,冰冻切片,进行双重免疫荧光染色,通过激光扫描共聚焦显微镜观察肺组织内是否存在DPCs。每例标本观察时镜下随机选择4~6个视野,计数100~200个肺细胞,得出每百个细胞内DPCs百分率,采用SPSS 11.0统计软件包对数据进行分析。结果:在成年鼠和新生鼠的正常肺组织中均发现了DPCs的存在,在人的肺腺癌组织中也发现了DPCs,而在鳞癌组织中未见DPCs;在人的癌旁组织DPCs数量明显多于相对应的癌组织(P<0.05)。结论:本研究不仅证实了DPCs细胞存在的广泛性,而且在人的肺腺癌组织中发现了DPCs,同时发现癌旁组织内的DPCs明显多于癌组织,为后续进一步分离、纯化DPCs,研究正常肺干细胞和肺癌干细胞的生物学特性提供了实验基础。
文摘Our understanding of hepatitis B virus(HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen(HBs Ag)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosisfactor(anti-TNF) and hematopoietic stem cell transplantation(HSCT). HBV reactivation could also occur in HBs Ag-negative, antibody to hepatitis B core antigen(anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBs Ag-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBs Ag-negative, antiHBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBs Ag-positive and HBs Ag-negative, anti-HBc positive individuals.
