Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several...Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).展开更多
Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironm...Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.展开更多
Current pharmacotherapies for Alzheimer's disease(AD)exhibit constrained transient symptomatic relief without halting underlying neurodegenerative progression.Based on the framework of the amyloid cascade and neur...Current pharmacotherapies for Alzheimer's disease(AD)exhibit constrained transient symptomatic relief without halting underlying neurodegenerative progression.Based on the framework of the amyloid cascade and neurofibrillary tangle hypotheses[1],two FDA-approved antiamyloid monoclonal antibodies(Aβ-mAbs),Kisunla and Lecanemab,have demonstrated efficacy in removing cerebral amyloid buildup,thereby modestly slowing cognitive decline in AD patients[2,3].A 2023 meta-analysis in Neurology demonstrated that anti-amyloid therapies significantly accelerated brain volume loss compared to placebo,with Lecanemab demonstrating 36.4%greater volume reduction and Donanemab 23%.展开更多
Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in million...Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.展开更多
In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnolo...In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes.However,their clinical success hinges significantly on overcoming drug delivery challenges related to stability,intracellular delivery,immunogenicity,and pharmacokinetic properties.Herein,we provide an overview of various marketed macromolecules,including nucleic acids,and immunotherapeutic agents such as cytokines and monoclonal antibodies,as well as other therapeutic peptides/proteins like enzymes,hormones,and coagulation factors.Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products,offering valuable insights for both scientific research and the pharmaceutical industry.展开更多
The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment(G)and fusion(F)glycoproteins with receptors on the cell surface.Langya henipavirus(LayV)was newly identifie...The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment(G)and fusion(F)glycoproteins with receptors on the cell surface.Langya henipavirus(LayV)was newly identified in China in 2022.The G proteins of LayV and Mojiang virus(MojV)exhibit high amino acid homology(86%),while they are located in a unique evolutionary clade within the Henipavirus genus.In this study,the crystal structure of the LayV G protein was resolved at a 3.37Åresolution,revealing a head domain with sixβ-propeller-like domains distinct from other henipavirus G proteins,such as those of Nipah virus(NiV)and Hendra virus(HeV).Furthermore,the prominent loop in the center cavity of the LayV G protein showed unique structural features.In the ELISA and SPR assays,the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor.Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein.These antibodies exhibited strong reactivity against both LayV and MojV G proteins.However,only weak cross-reactivity was observed with other henipaviruses.Moreover,eight monoclonal antibodies targeting the LayV G protein were generated,two of which exhibited broad binding activity across different henipavirus G proteins.These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses.展开更多
Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,...Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics.In this study,we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles(VLPs),both in vitro and in vivo.Using recombinant DNA technology,we engineered a baculovirus system to express EMCVs P12A and 3C,facilitating the production of VLPs in Sf9 cells.These VLPs serve as antigens to immunize mice,leading to the isolation of the monoclonal antibody 45G3.This antibody exhibited high specificity for EMCV confor-mational epitopes,excluding linear epitopes,and demonstrated potent in vitro neutralizing activity,with an IC50 of 0.01873μg/mL.Immunoelectron microscopy(IEM)revealed a strong direct interaction between the 45G3 antibody and EMCV particles.Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment,thereby preventing further infection of host cells.These findings further support the notion of a robust interaction between the virus and the antibody.Moreover,in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure.Additionally,posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain,indicating that the 45G3 antibody effectively blocked viral infection,thereby mitigating tissue damage and enhancing survival.These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.展开更多
Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlyi...Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.展开更多
Although African swine fever(ASF) has been prevalent for more than a century, it remains the number one swine disease that seriously endangers the global pig industry, and there is no effective means of prevention and...Although African swine fever(ASF) has been prevalent for more than a century, it remains the number one swine disease that seriously endangers the global pig industry, and there is no effective means of prevention and treatment(Wang et al. 2023). Due to its enormous economic and social impact, it is listed as a notifiable animal disease by the World Organization for Animal Health(Costard et al. 2013). Although ASF has been present in Sub-Saharan Africa since its first discovery in Kenya.展开更多
The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspe...The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.展开更多
Lumpy skin disease(LSD)is a highly contagious disease caused by lumpy skin disease virus(LSDV)in bovines.Rapid and accurate diagnosis is very important to controll it.However,current commercial detection kits need to ...Lumpy skin disease(LSD)is a highly contagious disease caused by lumpy skin disease virus(LSDV)in bovines.Rapid and accurate diagnosis is very important to controll it.However,current commercial detection kits need to be improved in terms of sensitivity or specificity.This study aimed to develop a novel diagnostic competitive enzyme-linked immunosorbent assay(cELISA)based on the newly identified antigen gene LSDV034.The rLSDV034 protein was identified as a potential diagnostic antigen,and it was expressed,purified,and used to immunize BALB/c mice.Using laboratory-prepared indirect ELISA(iELISA),the positive cell lines were screened,and their blocking activity was further verified by competitive ELISA(cELISA).The cell line,1H7,was chosen to produce mouse ascites,which were purified for a monoclonal antibody(mAb,5.395 mg/mL).The heavy chain type of the 1H7 mAb was identified as IgG1a,and its light chain subtype was identified as κ.Furthermore,cELISA was developed to detect bovine serum antibodies,with rLSDV034(4μg/mL)as the coating antigen and HRP-1H7 mAb(1:300)as the competitive antibody.The cutoff value of cELISA was 55%,based on 32 negative bovine serum samples.The analytical sensitivity was 1:8,and no cross-reaction was detected with bovine viral diarrhea virus(BVDV),infectious bovine rhinotracheitis virus(IBRV),Pasteurella multocida(P.multocida),or Mycoplasma bovis(M.bovis)from the serum samples.The diagnostic sensitivity and specificity of cELISA were 98.46%(95%confidence interval,CI:91.7–100)and 100%(95%CI:89.1–100),respectively,based on the analysis of 30 LSDV-infected bovine serum samples,35 GTPV-vaccinated samples,and 32 negative samples.The overall coincidence of the cELISA with the virus neutralization test(VNT)reached 98.97%(95%CI:94.4–100).Furthermore,we used cELISA to analyze 230 clinical bovine serum samples(including 59 infected and 171 vaccinated samples)and found that the serum positivity rates of the immunized samples(on d 60 postimmunization)and infected samples were 77.78%(95%CI:70.8–83.8%)and 71.19%(95%CI:57.9–82.2),respectively.These results indicate that the developed cELISA is promising for detecting serum antibodies in naturally infected or vaccinated cattle.展开更多
Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary ...Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary to develop an effective serological diagnostic tool for the surveillance of PDCoV infection and vaccine immunity effects.In this study,we developed a monoclonal antibody-based competitive ELISA(cELISA)that selected the purified recombinant PDCoV nucleocapsid(N)protein as the coating antigen to detect PDCoV antibodies.To evaluate the diagnostic performance of the cELISA,122 swine serum samples(39 positive and 83 negative)were tested and the results were compared with an indirect immunofluorescence assay(IFA)as the reference method.By receiver operating characteristic(ROC)curve analysis,the optimum cutoff value of percent inhibition(PI)was determined to be 26.8%,which showed excellent diagnostic performance,with an area under the curve(AUC)of 0.9919,a diagnostic sensitivity of 97.44%and a diagnostic specificity of 96.34%.Furthermore,there was good agreement between the cELISA and virus neutralization test(VNT)for the detection of PDCoV antibodies,with a coincidence rate of 92.7%,and theκanalysis showed almost perfect agreement(κ=0.851).Overall,the established cELISA showed good diagnostic performance,including sensitivity,specificity and repeatability,and can be used for diagnostic assistance,evaluating the response to vaccination and assessing swine herd immunity.展开更多
Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exite...Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exited into peripheral blood as a result of the dynamic interactions between the bone marrow(BM)microenvironment and neoplastic plasma cells.Chemokine receptors like chemokine receptor 4(CXCR4)and integrins are known to play a role in homing and migration of plasma cells(PCs).The hypoxic microenvironment in the BM niche also contributes to their circulation through various mechanisms.In addition,the CCL3–CCR1 axis probably competes with the retention signals from the CXCR4–α4β1(VLA-4)interaction and actively promotes the exit of PCs from the BM.CTPCs,even in extremely low numbers,can be detected and quantified by high-sensitivity techniques like multi-color flow cytometry and next-generation sequencing.High load of CTPCs noted in patients of plasma cell neoplasm;monoclonal gammopathy of undetermined significance(MGUS),smoldering multiple myeloma(SMM),multiple myeloma(MM)is a strong predictor of shorter progression free survival(PFS)as well as overall survival(OS).In newly diagnosed patients of MM,a load of CTPCs correlates with the outcomes,i.e.,OS and PFS.With more studies collaborating on the results of previous reports,assessment of the burden of CTPCs may become a complimentary approach for non-invasive risk stratification of MM patients and evaluating the response to therapy.Future research on larger cohorts and longer follow-ups may help to improve the existing staging system by incorporating the load of CTPCs as one of the prognostic indicators.Further studies based on isolation and genetic characterization of CTPCs may help in understanding the pathophysiology of the progression of the disease and may open avenues for newer treatment modalities.This review discusses the pathobiological aspects leading to circulation of neoplastic/tumor plasma cells in peripheral blood and provides a summary of research work done in last two decades on its prognostic importance in various plasma cells neoplasms.展开更多
Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and t...Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.展开更多
Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infec...Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infections are mild and self-limiting,they can cause severe or fatal illness,especially in children(Tracy and Gauntt,2008).展开更多
Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunogl...Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunoglobulin light chains(kappa and lambda)or transthyretin.[1]The clinical manifestations are mainly overlap with symptoms of other cardiovascular diseases mostly hypertrophic cardiomyopathy and heart failure.Some cases often overlooked and remains undiagnosed because of the atypical clinical manifestations,especially in the elderly.展开更多
Five monoclonal antibodies（Mabs） to nuclear protein of avain influenza virus（AIV） were developed by syncretizing SP 2/0 and the spleen cells from BALB of mice immuized with H9 subtype AIV. Specificity of these Mab...Five monoclonal antibodies（Mabs） to nuclear protein of avain influenza virus（AIV） were developed by syncretizing SP 2/0 and the spleen cells from BALB of mice immuized with H9 subtype AIV. Specificity of these Mabs were identified by immunofluorescent assay（IFA） and enzyme linked immunosorbent assay （ELISA）. These five Mabs which were named as AIV-NP-2C3, AIV-NP-6A5, AIV-NP-3 H9, AIV-NP-7B4, AIV-NP-2H4 could react with all viruses of AIV-H9 strains in tests. The result of Western blotting showed that only the 60 ku protein antigen of AIV-H9 could be recognized by the Mabs but never recognized by New castle disease virus, REV and infectious bursa disease virus. The result of preliminary application showed that avian influenza viruses could be deetected bv Mabs in IFA and ELISA. All these Mabs will probably play important roles in preventing and monitoring avian influenza viruses.展开更多
Mixed anhydride(MA)was used to conjugate ractopamine(RAC)to BSA and obtained artificial antigen BSA-RAC identified by UV and SDS-PAGE.Balb/c mice were immunized with BSA-RAC and hybridoma lines that secrete RAC monocl...Mixed anhydride(MA)was used to conjugate ractopamine(RAC)to BSA and obtained artificial antigen BSA-RAC identified by UV and SDS-PAGE.Balb/c mice were immunized with BSA-RAC and hybridoma lines that secrete RAC monoclonal antibody(mAb)were generated with cell fusion.A ciELISA kit for detection of RAC(RAC-Kit)was developed with RAC mAb and its performance were tested.The results indicated that BSA-RAC was successfully synthesized and its conjugation ratio of RAC to BSA was about 24.5∶1.Three hybridoma lines were filtered and the best one was 4D8-3E11,its affinity constant(Ka)was 1.65×1010 L/mol.The limit of detection of RAC-Kit was 0.5 ng/ml and its detection range was 0.5-184 ng/ml.The mean recoveries of RAC spiked in feed were 85.6% and in swine urine were 88.6%.The precision and accuracy of the assay as determined by inter-assay and intra-assay coefficient variation were below 15%.It had 9.4% cross-reactivity(CR%)to dobutamine and little or no CR to other compounds.The validity of RAC-Kit in 4 ℃ was in 180 d.展开更多
Using the purified VP1 protein of Asia 1 type foot-and-mouth disease virus as the antigen, the purified monoclonal antibody was labeled by the sodium periodate method and the monoclonal antibody competitive ELISA was ...Using the purified VP1 protein of Asia 1 type foot-and-mouth disease virus as the antigen, the purified monoclonal antibody was labeled by the sodium periodate method and the monoclonal antibody competitive ELISA was established in this study. Ten positive porcine foot-and-mouth disease serums and more than two hundreds negative serum were tested, and the results were the same as the background of samples. The sensitivity test and replicate test indicated that this method was stable and sensitive, which was suitable for monitoring Asia 1 type porcine foot-and-mouth disease virus antibody.展开更多
The production and characterization of a monoclonal antibody (MAb AB10) against GA 3 glucoside as well as GA 3 is described. MAb AB10 was derived from an immunogen in which human serum albumin (HSA) was linked to G...The production and characterization of a monoclonal antibody (MAb AB10) against GA 3 glucoside as well as GA 3 is described. MAb AB10 was derived from an immunogen in which human serum albumin (HSA) was linked to GA 3 at carbon 3. This antibody showed high affinity for GA 3 glucoside as well as for 13 hydroxy gibberellins (GA 1, GA 3, GA 5, etc). The affinity of MAb AB10 for 13 hydroxy GAs was significantly reduced by methylation of the 7 oic acid but not by glycosylation of 3 hydroxyl group. Based on this antibody, both of competitive enzyme linked immunosorbent assays (ELISAs) for GA 3 glucoside and for GA 3 were developed. These two ELISAs displayed linear detection ranges from 0 2 pmol to 20 pmol. Using these assays, the fluctuation of GA 3 like and GA 3 glucoside like substances in the leaves of Rumex japonicus was investigated. The results indicated that the glycosylation of free GAs was connected with leaf senescence and that the function of 6 benzyl amino purine in retarding the leaf senescence was probably related to delaying the process of glycosylation of free GAs.展开更多
文摘Neurodegenerative diseases are a growing burden on healthcare systems.Patients with Alzheimer’s or Parkinson’s diseases(AD or PD)are desperately waiting for innovative solutions that are slow to come,despite several decades of research worldwide.In 2021 and again in 2023,two monoclonal antibodies,aducanumab and lecanemab,have been approved by the U.S.Food and Drug Administration,and a third,donanemab,is currently under review.However,these treatments have very limited efficacy on cognitive functions and are accompanied by major side effects:amyloid-related imaging abnormalities,microhemorrhages,and accelerated brain volume loss(Høilund-Carlsen et al.,2024).
基金supported by the Kazan Federal University Strategic Academic Leadership Program(PRIORITY-2030).
文摘Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.
基金supported by the Research Personnel Cultivation Programme of Zhongda Hospital Southeast(CZXM-GSP-RC172)the Science and Technology Innovation 2030 Major Projects(2022ZD0211600)the National Natural Science Foundation of China(82271574 and 82502335).
文摘Current pharmacotherapies for Alzheimer's disease(AD)exhibit constrained transient symptomatic relief without halting underlying neurodegenerative progression.Based on the framework of the amyloid cascade and neurofibrillary tangle hypotheses[1],two FDA-approved antiamyloid monoclonal antibodies(Aβ-mAbs),Kisunla and Lecanemab,have demonstrated efficacy in removing cerebral amyloid buildup,thereby modestly slowing cognitive decline in AD patients[2,3].A 2023 meta-analysis in Neurology demonstrated that anti-amyloid therapies significantly accelerated brain volume loss compared to placebo,with Lecanemab demonstrating 36.4%greater volume reduction and Donanemab 23%.
文摘Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.
基金supported by the National Natural Science Foundation of China(Nos.82073782 and 82241002)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.21KJA320003)the Scientific Research Project of Jiangsu Commission of Health(No.LKZ2023001)。
文摘In recent years,biopharmaceuticals have witnessed remarkable advancements,transforming the landscape of therapeutic interventions.Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes.However,their clinical success hinges significantly on overcoming drug delivery challenges related to stability,intracellular delivery,immunogenicity,and pharmacokinetic properties.Herein,we provide an overview of various marketed macromolecules,including nucleic acids,and immunotherapeutic agents such as cytokines and monoclonal antibodies,as well as other therapeutic peptides/proteins like enzymes,hormones,and coagulation factors.Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products,offering valuable insights for both scientific research and the pharmaceutical industry.
基金the funding support from the National Natural Science Foundation of China(32200762).
文摘The invasion of host cells by the henipavirus is facilitated through the interaction between viral attachment(G)and fusion(F)glycoproteins with receptors on the cell surface.Langya henipavirus(LayV)was newly identified in China in 2022.The G proteins of LayV and Mojiang virus(MojV)exhibit high amino acid homology(86%),while they are located in a unique evolutionary clade within the Henipavirus genus.In this study,the crystal structure of the LayV G protein was resolved at a 3.37Åresolution,revealing a head domain with sixβ-propeller-like domains distinct from other henipavirus G proteins,such as those of Nipah virus(NiV)and Hendra virus(HeV).Furthermore,the prominent loop in the center cavity of the LayV G protein showed unique structural features.In the ELISA and SPR assays,the LayV G protein was unable to bind to the existing henipavirus-neutralizing antibodies or the ephrin-B2 receptor.Immunogenicity studies in mice demonstrated robust antibody responses elicited by the LayV G protein.These antibodies exhibited strong reactivity against both LayV and MojV G proteins.However,only weak cross-reactivity was observed with other henipaviruses.Moreover,eight monoclonal antibodies targeting the LayV G protein were generated,two of which exhibited broad binding activity across different henipavirus G proteins.These findings underscore the need for tailored vaccines and therapeutics for LayV and related novel henipaviruses.
基金funded by the National Key Research and Development Program of China(grant number:2023YFC2306501)the Hubei Provincial Fund for Supporting High-Quality Development of the Seed Industry"Conservation and Utilization of Agricultural Germplasm Resources"Project(grant number:HBZY2023A001-16)。
文摘Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics.In this study,we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles(VLPs),both in vitro and in vivo.Using recombinant DNA technology,we engineered a baculovirus system to express EMCVs P12A and 3C,facilitating the production of VLPs in Sf9 cells.These VLPs serve as antigens to immunize mice,leading to the isolation of the monoclonal antibody 45G3.This antibody exhibited high specificity for EMCV confor-mational epitopes,excluding linear epitopes,and demonstrated potent in vitro neutralizing activity,with an IC50 of 0.01873μg/mL.Immunoelectron microscopy(IEM)revealed a strong direct interaction between the 45G3 antibody and EMCV particles.Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment,thereby preventing further infection of host cells.These findings further support the notion of a robust interaction between the virus and the antibody.Moreover,in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure.Additionally,posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain,indicating that the 45G3 antibody effectively blocked viral infection,thereby mitigating tissue damage and enhancing survival.These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.
文摘Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.
基金supported by the National Key Research and Development Program of China (2021YFD1800100)the earmarked fund for China Agriculture Research System (CARS-35)。
文摘Although African swine fever(ASF) has been prevalent for more than a century, it remains the number one swine disease that seriously endangers the global pig industry, and there is no effective means of prevention and treatment(Wang et al. 2023). Due to its enormous economic and social impact, it is listed as a notifiable animal disease by the World Organization for Animal Health(Costard et al. 2013). Although ASF has been present in Sub-Saharan Africa since its first discovery in Kenya.
文摘The monoclonal antibodies consist of an innovative form of immunotherapy,capable of defeating several diseases,such as cancer.It is an emergent and important theme,that advances evaluation,challenges,and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research.Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials,which were selected between 2022 and 2023,in order to understand better the monoclonal antibodies that were most studied.The biopharmaceutical compounds Ibrutinib,Obinutuzumab,Rituximab,Venetoclax,and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications,indicating the importance of amplifying the studies.The action mechanisms that are used imply that their combined use has more success in the disease remission,showing a lower recurrence,adverse effects,and toxicity.Besides the adverse effects and overwhelming prices of the treatment,these immunotherapies results are promising,amplifying the survival rates,improving the patient’s life quality,and resulting in a precision medicine,aiming a custom treatment.The future perspectives on this therapy consist of its application in the public health system,with patients being able to be submitted to this treatment without any costs and receive a better life quality.
基金financially supported by the National Key Research and Development Program of China(#2022YFD1800701)the Key Research and Development Program of the Ningxia Hui Autonomous Region(#2021BEF02028)the Chinese Agricultural Research System of MOF and MARA(#CARS-37).
文摘Lumpy skin disease(LSD)is a highly contagious disease caused by lumpy skin disease virus(LSDV)in bovines.Rapid and accurate diagnosis is very important to controll it.However,current commercial detection kits need to be improved in terms of sensitivity or specificity.This study aimed to develop a novel diagnostic competitive enzyme-linked immunosorbent assay(cELISA)based on the newly identified antigen gene LSDV034.The rLSDV034 protein was identified as a potential diagnostic antigen,and it was expressed,purified,and used to immunize BALB/c mice.Using laboratory-prepared indirect ELISA(iELISA),the positive cell lines were screened,and their blocking activity was further verified by competitive ELISA(cELISA).The cell line,1H7,was chosen to produce mouse ascites,which were purified for a monoclonal antibody(mAb,5.395 mg/mL).The heavy chain type of the 1H7 mAb was identified as IgG1a,and its light chain subtype was identified as κ.Furthermore,cELISA was developed to detect bovine serum antibodies,with rLSDV034(4μg/mL)as the coating antigen and HRP-1H7 mAb(1:300)as the competitive antibody.The cutoff value of cELISA was 55%,based on 32 negative bovine serum samples.The analytical sensitivity was 1:8,and no cross-reaction was detected with bovine viral diarrhea virus(BVDV),infectious bovine rhinotracheitis virus(IBRV),Pasteurella multocida(P.multocida),or Mycoplasma bovis(M.bovis)from the serum samples.The diagnostic sensitivity and specificity of cELISA were 98.46%(95%confidence interval,CI:91.7–100)and 100%(95%CI:89.1–100),respectively,based on the analysis of 30 LSDV-infected bovine serum samples,35 GTPV-vaccinated samples,and 32 negative samples.The overall coincidence of the cELISA with the virus neutralization test(VNT)reached 98.97%(95%CI:94.4–100).Furthermore,we used cELISA to analyze 230 clinical bovine serum samples(including 59 infected and 171 vaccinated samples)and found that the serum positivity rates of the immunized samples(on d 60 postimmunization)and infected samples were 77.78%(95%CI:70.8–83.8%)and 71.19%(95%CI:57.9–82.2),respectively.These results indicate that the developed cELISA is promising for detecting serum antibodies in naturally infected or vaccinated cattle.
基金supported by the National Key Research and Development Program(2023YFD1800501)the National Natural Science Foundation of China(32373030,32202787)+5 种基金the S&T Program of Hebei(21322401D)the Jiangsu Province Natural Sciences Foundation(BK20221432,BK20210158)the Jiangsu Agricultural Science and Technology Innovation Fund(CX(22)3028)the Special Project of Northern Jiangsu(SZ-LYG202109)the Open Fund of Shaoxing Academy of Biomedicine of Zhejiang Sci-Tech University(SXAB202215)the Open Fund of Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases,Ministry of Agriculture and Rural Affairs(YDWS202213).
文摘Porcine deltacoronavirus(PDCoV)is an emerging swine enteropathogenic coronavirus that can cause acute diarrhea and vomiting in newborn piglets and poses a potential risk for cross-species transmission.It is necessary to develop an effective serological diagnostic tool for the surveillance of PDCoV infection and vaccine immunity effects.In this study,we developed a monoclonal antibody-based competitive ELISA(cELISA)that selected the purified recombinant PDCoV nucleocapsid(N)protein as the coating antigen to detect PDCoV antibodies.To evaluate the diagnostic performance of the cELISA,122 swine serum samples(39 positive and 83 negative)were tested and the results were compared with an indirect immunofluorescence assay(IFA)as the reference method.By receiver operating characteristic(ROC)curve analysis,the optimum cutoff value of percent inhibition(PI)was determined to be 26.8%,which showed excellent diagnostic performance,with an area under the curve(AUC)of 0.9919,a diagnostic sensitivity of 97.44%and a diagnostic specificity of 96.34%.Furthermore,there was good agreement between the cELISA and virus neutralization test(VNT)for the detection of PDCoV antibodies,with a coincidence rate of 92.7%,and theκanalysis showed almost perfect agreement(κ=0.851).Overall,the established cELISA showed good diagnostic performance,including sensitivity,specificity and repeatability,and can be used for diagnostic assistance,evaluating the response to vaccination and assessing swine herd immunity.
文摘Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exited into peripheral blood as a result of the dynamic interactions between the bone marrow(BM)microenvironment and neoplastic plasma cells.Chemokine receptors like chemokine receptor 4(CXCR4)and integrins are known to play a role in homing and migration of plasma cells(PCs).The hypoxic microenvironment in the BM niche also contributes to their circulation through various mechanisms.In addition,the CCL3–CCR1 axis probably competes with the retention signals from the CXCR4–α4β1(VLA-4)interaction and actively promotes the exit of PCs from the BM.CTPCs,even in extremely low numbers,can be detected and quantified by high-sensitivity techniques like multi-color flow cytometry and next-generation sequencing.High load of CTPCs noted in patients of plasma cell neoplasm;monoclonal gammopathy of undetermined significance(MGUS),smoldering multiple myeloma(SMM),multiple myeloma(MM)is a strong predictor of shorter progression free survival(PFS)as well as overall survival(OS).In newly diagnosed patients of MM,a load of CTPCs correlates with the outcomes,i.e.,OS and PFS.With more studies collaborating on the results of previous reports,assessment of the burden of CTPCs may become a complimentary approach for non-invasive risk stratification of MM patients and evaluating the response to therapy.Future research on larger cohorts and longer follow-ups may help to improve the existing staging system by incorporating the load of CTPCs as one of the prognostic indicators.Further studies based on isolation and genetic characterization of CTPCs may help in understanding the pathophysiology of the progression of the disease and may open avenues for newer treatment modalities.This review discusses the pathobiological aspects leading to circulation of neoplastic/tumor plasma cells in peripheral blood and provides a summary of research work done in last two decades on its prognostic importance in various plasma cells neoplasms.
基金funded by the Beijing Natural Science Foundation(5242007,L222076,L246011)the High-level Public Health Technical Talents Project by the Beijing Municipal Commission of Health(Key discipline personnel-02-05)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-12M-5-026,2022-I2M-CoV19-006)the Reform and Development of the Beijing Municipal Health Commission,and the Respiratory Research Project of the National Clinical Research Center for Respiratory Diseases(HXZX-202106).
文摘Respiratory syncytial virus(RSV)is one of the most common viruses leading to lower respiratory tract infections(LRTIs)in children and elderly individuals worldwide.Although significant progress in the prevention and treatment of RSV infection was made in 2023,with two anti-RSV vaccines and one monoclonal antibody approved by the FDA,there is still a lack of postinfection therapeutic drugs in clinical practice,especially for the pediatric population.In recent years,with an increasing understanding of the pathogenic mechanisms of RSV,drugs and drug candidates,have shown great potential for clinical application.In this review,we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.
基金supported by grants from the National Natural Science Foundation of China(82172248,82472253,82272310 and 32470996)the Xiamen Science and Technology Program(2022CXY0102)+1 种基金the Fundamental Research Funds for the Central Universities(20720250004)the Independent Research Project of the State Key Laboratory of Vaccine for Infectious Diseases(2024SKLVDzy03).
文摘Dear Editor,Group B coxsackieviruses(CVBs),belonging to the genus Enterovirus(EV)of the family Picornaviridae,comprise six serotypes and share a typical picornaviral structure(Alhazmi et al.,2023).While most CVB infections are mild and self-limiting,they can cause severe or fatal illness,especially in children(Tracy and Gauntt,2008).
基金supported by the National Clinical Research Center for Geriatric Diseases Foundation of Chinese PLA General Hospital(NCRCG-PLAGH-2024007).
文摘Cardiac amyloidosis(CA)is characterized by the deposition of the misfolded amyloid precursor proteins in the myocardium of the heart.The systemic form of CA is mainly caused by either the misfolded monoclonal immunoglobulin light chains(kappa and lambda)or transthyretin.[1]The clinical manifestations are mainly overlap with symptoms of other cardiovascular diseases mostly hypertrophic cardiomyopathy and heart failure.Some cases often overlooked and remains undiagnosed because of the atypical clinical manifestations,especially in the elderly.
基金Supported by the National Key Technologies Research and Develop-ment Program of China during the 10th Five-Year Plan Period(2004BA519A05)Technologies Research and Development Program of China during the 10th Five-Year Plan Period in Jiangsu Province(BE2002346).~~
文摘Five monoclonal antibodies（Mabs） to nuclear protein of avain influenza virus（AIV） were developed by syncretizing SP 2/0 and the spleen cells from BALB of mice immuized with H9 subtype AIV. Specificity of these Mabs were identified by immunofluorescent assay（IFA） and enzyme linked immunosorbent assay （ELISA）. These five Mabs which were named as AIV-NP-2C3, AIV-NP-6A5, AIV-NP-3 H9, AIV-NP-7B4, AIV-NP-2H4 could react with all viruses of AIV-H9 strains in tests. The result of Western blotting showed that only the 60 ku protein antigen of AIV-H9 could be recognized by the Mabs but never recognized by New castle disease virus, REV and infectious bursa disease virus. The result of preliminary application showed that avian influenza viruses could be deetected bv Mabs in IFA and ELISA. All these Mabs will probably play important roles in preventing and monitoring avian influenza viruses.
基金Supported by the Key Project of National Science and Technology Surporting Plan during 11th-Five-Year of China(2006BAK02A21/1)~~
文摘Mixed anhydride(MA)was used to conjugate ractopamine(RAC)to BSA and obtained artificial antigen BSA-RAC identified by UV and SDS-PAGE.Balb/c mice were immunized with BSA-RAC and hybridoma lines that secrete RAC monoclonal antibody(mAb)were generated with cell fusion.A ciELISA kit for detection of RAC(RAC-Kit)was developed with RAC mAb and its performance were tested.The results indicated that BSA-RAC was successfully synthesized and its conjugation ratio of RAC to BSA was about 24.5∶1.Three hybridoma lines were filtered and the best one was 4D8-3E11,its affinity constant(Ka)was 1.65×1010 L/mol.The limit of detection of RAC-Kit was 0.5 ng/ml and its detection range was 0.5-184 ng/ml.The mean recoveries of RAC spiked in feed were 85.6% and in swine urine were 88.6%.The precision and accuracy of the assay as determined by inter-assay and intra-assay coefficient variation were below 15%.It had 9.4% cross-reactivity(CR%)to dobutamine and little or no CR to other compounds.The validity of RAC-Kit in 4 ℃ was in 180 d.
基金Supported by National High-tech R&D Program (863) Subsidized Project(2006AA10A204)Special Fund for Basic Scientific Research-related Subsidy of State-level and Public-welfare Scientific Research Institutes~~
文摘Using the purified VP1 protein of Asia 1 type foot-and-mouth disease virus as the antigen, the purified monoclonal antibody was labeled by the sodium periodate method and the monoclonal antibody competitive ELISA was established in this study. Ten positive porcine foot-and-mouth disease serums and more than two hundreds negative serum were tested, and the results were the same as the background of samples. The sensitivity test and replicate test indicated that this method was stable and sensitive, which was suitable for monitoring Asia 1 type porcine foot-and-mouth disease virus antibody.
文摘The production and characterization of a monoclonal antibody (MAb AB10) against GA 3 glucoside as well as GA 3 is described. MAb AB10 was derived from an immunogen in which human serum albumin (HSA) was linked to GA 3 at carbon 3. This antibody showed high affinity for GA 3 glucoside as well as for 13 hydroxy gibberellins (GA 1, GA 3, GA 5, etc). The affinity of MAb AB10 for 13 hydroxy GAs was significantly reduced by methylation of the 7 oic acid but not by glycosylation of 3 hydroxyl group. Based on this antibody, both of competitive enzyme linked immunosorbent assays (ELISAs) for GA 3 glucoside and for GA 3 were developed. These two ELISAs displayed linear detection ranges from 0 2 pmol to 20 pmol. Using these assays, the fluctuation of GA 3 like and GA 3 glucoside like substances in the leaves of Rumex japonicus was investigated. The results indicated that the glycosylation of free GAs was connected with leaf senescence and that the function of 6 benzyl amino purine in retarding the leaf senescence was probably related to delaying the process of glycosylation of free GAs.
