Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel ...Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.展开更多
Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The m...Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.展开更多
Based on the theory of long distance interaction between antibodies and antigens we developed a theory of affinity maturation of antibodies that is based on longitudinale electric waves. Early stage antibodies show a ...Based on the theory of long distance interaction between antibodies and antigens we developed a theory of affinity maturation of antibodies that is based on longitudinale electric waves. Early stage antibodies show a wide frequency spectrum for antigens and are polyspecific. After affinity maturation the antibody shows a very narrow band spectrum, the antibodies become monospecific. The feedback between antibody and antibody producing cell is done via messenger molecules that are also communicating with help of longitudinal electric waves. These messenger molecules transfer information from antibody arms and are informing cells whether the epitopes are switched on or off. The folding of antibody is done via eigen frequency resonances.展开更多
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is curable with first-line chemoimmunotherapy but patients with relapsed/refractory(R/R)DLBCL still face a poor prognosis.For patients with R/R DLBCL,the complete respons...BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is curable with first-line chemoimmunotherapy but patients with relapsed/refractory(R/R)DLBCL still face a poor prognosis.For patients with R/R DLBCL,the complete response rate to traditional next-line therapy is only 7%and the median overall survival is 6.3 mo.Recently,CD19-targeting chimeric antigen receptor T cells(CAR-T)have shown promise in clinical trials.However,approximately 50%of patients treated with CAR-T cells ultimately progress and few salvage therapies are effective.CASE SUMMARY Here,we report on 7 patients with R/R DLBCL whose disease progressed after CAR-T infusion.They received a PD-1 inhibitor(sintilimab)and a histone deacetylase inhibitor(chidamide).Five of the 7 patients tolerated the treatment without any serious adverse events.Two patients discontinued the treatment due to lung infection and rash.At the 20-mo follow-up,the median overall survival of these 7 patients was 6 mo.Of note,there were 2 complete response rates(CRs)and 2 partial response rates(PRs)during this novel therapy,with an overall response rate(ORR)of 57.1%,and one patient had a durable CR that lasted at least 20 mo.CONCLUSION In conclusion,chidamide combined with sintilimab may be a choice for DLBCL patients progressing after CD19-targeting CAR-T therapy.展开更多
Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes w...Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes were identified using in silico B-cell epitope prediction.A synthetic peptide analog of the predicted epitope was used to induce antipeptide IgY production in hens which was purified using affinity chromatography.Presence of purified IgY and its binding specificity were performed by gel electrophoresis and ELISA,respectively.Results:Out of the nine continuous epitopes identified,the sequence at position 193-208(LKVREDYSLECDPAVI)was selected and used to produce anti-peptide IgY.The produced IgY was found to bind to the synthetic analog of the Zika virus NS1 immunogenic epitope but not to other flaviviruses and random peptides from other pathogens.Conclusions:In this study,we identified an immunogenic epitope unique to Zika virus that can be used to develop a serodiagnostic tool that specifically detect Zika virus infection.展开更多
In this paper,we present the effective distance between T-cell and B-cell in an immune system using Stop and Wait(S/W)Automatic Repeat Request(ARQ).The concentration of the molecules can be increased by increasing the...In this paper,we present the effective distance between T-cell and B-cell in an immune system using Stop and Wait(S/W)Automatic Repeat Request(ARQ).The concentration of the molecules can be increased by increasing the transmitting number of molecules but it may reduce the performance of communication due to higher collision or interference with other molecules.It is also reported in the literature that the concentration of the emitted molecules reduces if the distance from Transmitter(Tx)to Receiver(Rx)increases.Thus,this paper mainly focuses on enhancing the receiver’s capture probability and higher successful complete transmission of the desired molecules by obtaining the effective distance from T-cell to B-cell.In order to find the effective distance,T-cell transmits the molecules 1(Interleukins-2)to B-cell,upon successful reception of molecules 1,antibodies(molecules 2)transmit back to T-cell.Then,the effective distance of an immune system can be obtained after T-cell detects the concentration of the molecules 2 with respect to time.Different schemes of S/W ARQ protocols have implemented in Molecular Communication(MC)but it requires retransmission of duplicate copies due to the lack of addressing an effective distance.Thus,the simulations are performed in MATLAB and the results obtain higher capture probability and also successful complete transmission of the desired molecules.展开更多
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing ap...BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.展开更多
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
B细胞成熟抗原(BCMA)是B淋巴细胞刺激因子(BLyS)的受体之一.它的胞外区与人IgG1Fc的融合蛋白eBCMA-Fc,又称为诱饵受体,具有拮抗BLyS的活性.为了设计新的拮抗肽,基于BCMA和Fc的晶体结构,通过计算机图形学技术、分子模拟方法,建立了eBCMA...B细胞成熟抗原(BCMA)是B淋巴细胞刺激因子(BLyS)的受体之一.它的胞外区与人IgG1Fc的融合蛋白eBCMA-Fc,又称为诱饵受体,具有拮抗BLyS的活性.为了设计新的拮抗肽,基于BCMA和Fc的晶体结构,通过计算机图形学技术、分子模拟方法,建立了eBCMA-Fc融合蛋白的三维理论结构.利用均方根位移(root mean square distance,RMSD)对eBCMA-Fc融合蛋白与单体eBCMA、Fc构象差异进行分析.融合蛋白eBCMA-Fc中的eBCMA段与单体eBCMA的主链碳原子间RMSD值为0.036nm,Fc段与单体Fc的主链碳原子间RMSD值为0.064nm.结果表明,对比单体,融合蛋白eBCMA-Fc并未因eBCMA与Fc直接连接而发生构象的变化.分子对接方法显示,融合蛋白eBCMA-Fc中的BCMA与BLyS作用,而Fc扮演着稳定BCMA构象的支架作用.为进一步验证上述理论分析,构建eBCMA-Fc融合基因,并将载有eBCMA-Fc融合基因的原核表达质粒转化BL21(DE3)菌、在细菌中表达.目的蛋白经蛋白A亲和柱纯化大约为36kD,与理论预测值34kD相近.免疫印迹表明抗人IgG抗体能够识别eBCMA-Fc融合蛋白.ELISA证实,eBCMA-Fc融合蛋白能够结合BLyS.随着eBCMA-Fc融合蛋白增加,结合BLyS的融合蛋白也相应增加.而对照人IgG,即使在高浓度条件下,也不结合BLyS.此外,eBCMA-Fc融合蛋白能够抑制BLyS对B细胞肿瘤Daudi细胞的作用.这些研究为下一步设计和筛选BLyS拮抗肽提供了实验基础.展开更多
文摘Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.
基金supported by the Natural Science Foundation of Zhejiang Province(Q23C180006)the Zhejiang A&F University Talent Initiative Project(118-203402005901).
文摘Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.
文摘Based on the theory of long distance interaction between antibodies and antigens we developed a theory of affinity maturation of antibodies that is based on longitudinale electric waves. Early stage antibodies show a wide frequency spectrum for antigens and are polyspecific. After affinity maturation the antibody shows a very narrow band spectrum, the antibodies become monospecific. The feedback between antibody and antibody producing cell is done via messenger molecules that are also communicating with help of longitudinal electric waves. These messenger molecules transfer information from antibody arms and are informing cells whether the epitopes are switched on or off. The folding of antibody is done via eigen frequency resonances.
文摘BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is curable with first-line chemoimmunotherapy but patients with relapsed/refractory(R/R)DLBCL still face a poor prognosis.For patients with R/R DLBCL,the complete response rate to traditional next-line therapy is only 7%and the median overall survival is 6.3 mo.Recently,CD19-targeting chimeric antigen receptor T cells(CAR-T)have shown promise in clinical trials.However,approximately 50%of patients treated with CAR-T cells ultimately progress and few salvage therapies are effective.CASE SUMMARY Here,we report on 7 patients with R/R DLBCL whose disease progressed after CAR-T infusion.They received a PD-1 inhibitor(sintilimab)and a histone deacetylase inhibitor(chidamide).Five of the 7 patients tolerated the treatment without any serious adverse events.Two patients discontinued the treatment due to lung infection and rash.At the 20-mo follow-up,the median overall survival of these 7 patients was 6 mo.Of note,there were 2 complete response rates(CRs)and 2 partial response rates(PRs)during this novel therapy,with an overall response rate(ORR)of 57.1%,and one patient had a durable CR that lasted at least 20 mo.CONCLUSION In conclusion,chidamide combined with sintilimab may be a choice for DLBCL patients progressing after CD19-targeting CAR-T therapy.
文摘Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes were identified using in silico B-cell epitope prediction.A synthetic peptide analog of the predicted epitope was used to induce antipeptide IgY production in hens which was purified using affinity chromatography.Presence of purified IgY and its binding specificity were performed by gel electrophoresis and ELISA,respectively.Results:Out of the nine continuous epitopes identified,the sequence at position 193-208(LKVREDYSLECDPAVI)was selected and used to produce anti-peptide IgY.The produced IgY was found to bind to the synthetic analog of the Zika virus NS1 immunogenic epitope but not to other flaviviruses and random peptides from other pathogens.Conclusions:In this study,we identified an immunogenic epitope unique to Zika virus that can be used to develop a serodiagnostic tool that specifically detect Zika virus infection.
基金“Visvesvaraya Ph. D Scheme”, Govt. of India to give us an opportunity to complete this paper with their financial support
文摘In this paper,we present the effective distance between T-cell and B-cell in an immune system using Stop and Wait(S/W)Automatic Repeat Request(ARQ).The concentration of the molecules can be increased by increasing the transmitting number of molecules but it may reduce the performance of communication due to higher collision or interference with other molecules.It is also reported in the literature that the concentration of the emitted molecules reduces if the distance from Transmitter(Tx)to Receiver(Rx)increases.Thus,this paper mainly focuses on enhancing the receiver’s capture probability and higher successful complete transmission of the desired molecules by obtaining the effective distance from T-cell to B-cell.In order to find the effective distance,T-cell transmits the molecules 1(Interleukins-2)to B-cell,upon successful reception of molecules 1,antibodies(molecules 2)transmit back to T-cell.Then,the effective distance of an immune system can be obtained after T-cell detects the concentration of the molecules 2 with respect to time.Different schemes of S/W ARQ protocols have implemented in Molecular Communication(MC)but it requires retransmission of duplicate copies due to the lack of addressing an effective distance.Thus,the simulations are performed in MATLAB and the results obtain higher capture probability and also successful complete transmission of the desired molecules.
文摘BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
文摘B细胞成熟抗原(BCMA)是B淋巴细胞刺激因子(BLyS)的受体之一.它的胞外区与人IgG1Fc的融合蛋白eBCMA-Fc,又称为诱饵受体,具有拮抗BLyS的活性.为了设计新的拮抗肽,基于BCMA和Fc的晶体结构,通过计算机图形学技术、分子模拟方法,建立了eBCMA-Fc融合蛋白的三维理论结构.利用均方根位移(root mean square distance,RMSD)对eBCMA-Fc融合蛋白与单体eBCMA、Fc构象差异进行分析.融合蛋白eBCMA-Fc中的eBCMA段与单体eBCMA的主链碳原子间RMSD值为0.036nm,Fc段与单体Fc的主链碳原子间RMSD值为0.064nm.结果表明,对比单体,融合蛋白eBCMA-Fc并未因eBCMA与Fc直接连接而发生构象的变化.分子对接方法显示,融合蛋白eBCMA-Fc中的BCMA与BLyS作用,而Fc扮演着稳定BCMA构象的支架作用.为进一步验证上述理论分析,构建eBCMA-Fc融合基因,并将载有eBCMA-Fc融合基因的原核表达质粒转化BL21(DE3)菌、在细菌中表达.目的蛋白经蛋白A亲和柱纯化大约为36kD,与理论预测值34kD相近.免疫印迹表明抗人IgG抗体能够识别eBCMA-Fc融合蛋白.ELISA证实,eBCMA-Fc融合蛋白能够结合BLyS.随着eBCMA-Fc融合蛋白增加,结合BLyS的融合蛋白也相应增加.而对照人IgG,即使在高浓度条件下,也不结合BLyS.此外,eBCMA-Fc融合蛋白能够抑制BLyS对B细胞肿瘤Daudi细胞的作用.这些研究为下一步设计和筛选BLyS拮抗肽提供了实验基础.
