Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte...Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.展开更多
BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with A...BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.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
Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst m...Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.展开更多
To determine how the auto-antibodies(Abs)profiles overlap in chronic hepatitis C infection(CHC)and autoimmune hepatitis(AIH)and correlate to liver disease.METHODSLevels of antinuclear Ab,smooth muscle antibody(SMA)and...To determine how the auto-antibodies(Abs)profiles overlap in chronic hepatitis C infection(CHC)and autoimmune hepatitis(AIH)and correlate to liver disease.METHODSLevels of antinuclear Ab,smooth muscle antibody(SMA)and liver/kidney microsomal-1(LKM-1)Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection,20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG,alkaline phosphatase,total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies(auto-Abs)than CHC patients.Antinuclear Ab,SMA and LKM-1 Ab were also present in 36%of CHC patients and related to disease severity.CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG.These cases had longer disease duration compared with auto-Ab negative cases,but there was no difference in gender,age or viral load.KLM-1<sup>+</sup>Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH.Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage.Future studies will unravel any novel associations between these two diseases,whether genetic or other.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
Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safet...Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.展开更多
Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of pat...Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of patients with metastatic UC(mUC)remains poor(10-15%)2.展开更多
Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Insp...Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Inspired by the great success of artificial intelligence-based algorithms,especially deep learning-based methods in the field of biology,various computational methods have been introduced into antibody optimization to reduce costs and increase the success rate of lead candidate generation and optimization.Herein,we briefly review recent progress in deep learning-based antibody optimization,focusing on the available datasets and algorithm input data types that are crucial for constructing appropriate deep learning models.Furthermore,we discuss the current challenges and potential solutions for the future development of general-purpose deep learning algorithms in antibody optimization.展开更多
Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces pati...Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.展开更多
BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impa...BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.展开更多
Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrh...Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrhagic stroke remains unknown.This study aimed to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and hemorrhagic stroke using the two-sample Mendelian randomization(MR)method.Comprehensive analyses were conducted using publicly available data from genome-wide association study(GWAS),which involved the whole genomes of 9724 European participants and 46 antibody measurement phenotypes,and summary statistics from the FinnGen dataset R12(including intracerebral hemorrhage and subarachnoid hemorrhage)were used.The causal relationship between the aforementioned immune responses and hemorrhagic stroke was analyzed using inverse-variance weighting,MR-Egger regression,weighted median,weighted mode,simple mode,and MR-pleiotropy residual sum and outlier(MR-PRESSO),while various sensitivity analyses were performed to assess heterogeneity and pleiotropy in the study findings.Results showed that human herpes virus 7(HHV-7)U14 antibody levels(OR:0.877,95%CI:0.797-0.964,P=0.007)exerted a protective effect against hemorrhagic stroke,and Chlamydia trachomatis(CT)tarp-D F2 antibody levels(OR:0.937,95%CI:0.885-0.992,P=0.025)had a potential protective effect;additionally,Epstein-Barr virus(EBV)ZEBRA antibody levels(OR:1.062,95%CI:1.012-1.114,P=0.014),human herpesvirus 6(HHV-6)p101k antibody levels(OR:1.054,95%CI:1.002-1.108,P=0.042),and cytomegalovirus(CMV)pp150 antibody levels(OR:1.086,95%CI:1.002-1.176,P=0.045)were potential risk factors for the disease.No significant pleiotropy or heterogeneity was observed in any of the MR analyses.Collectively,these findings confirmed a significant causal relationship between antibody-mediated immune responses and hemorrhagic stroke,and this study contributed to a deeper understanding of the potential mechanisms underlying hemorrhagic stroke onset.展开更多
The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer i...The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.展开更多
BACKGROUND Hepatitis B virus(HBV)infection is a leading cause of global hepatocellular carcinoma(HCC).Conventional biomarkers such as alpha-fetoprotein(AFP)demonstrate suboptimal sensitivity and specificity.Emerging e...BACKGROUND Hepatitis B virus(HBV)infection is a leading cause of global hepatocellular carcinoma(HCC).Conventional biomarkers such as alpha-fetoprotein(AFP)demonstrate suboptimal sensitivity and specificity.Emerging evidence suggests that serum extra spindle pole bodies like 1(ESPL1)protein and p53 antibody may improve diagnostic accuracy.AIM To assess and compare the diagnostic performance of serum ESPL1 protein and p53 antibody in HBV-related HCC(HBV-HCC).METHODS This case-control study from the First Affiliated Hospital of Guangxi Medical University enrolled 30 patients with chronic hepatitis B(CHB),30 with HBV-related liver cirrhosis(HBV-LC),55 with HBV-HCC,and 30 healthy controls.Serum ESPL1 protein and p53 antibody levels were quantified via ELISA.Diagnostic performance was evaluated using receiver operating characteristic(ROC)curve analysis,including sensitivity,specificity,and correlation with AFP.RESULTS Serum ESPL1 protein levels progressively increased across disease stages(CHB:89.9 ng/L;HBV-LC:188.83 ng/L;HBV-HCC:317.63 ng/L),with a significantly higher area under the ROC curve(AUC=0.917)than either p53 antibody(AUC=0.725)or AFP(AUC=0.678).p53 antibody levels were significantly elevated only in the HBVHCC group.ESPL1 demonstrated superior sensitivity and concordance with histopathological findings.A significant correlation between ESPL1 and p53 antibody levels was observed exclusively in the HBV-HCC group(r=0.320,P=0.017),suggesting potential interplay in malignant transformation.CONCLUSION Serum ESPL1 protein,a promising biomarker for early HBV-HCC detection,outperforms p53 antibody in diagnostic reliability.Higher ESPL1 levels correlate with increased HCC risk in chronic HBV patients.展开更多
DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expressi...DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).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
Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, ...Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.展开更多
[Objectives]This study was conducted to evaluate the immunization efficacy and infection status of classical swine fever(CSF),foot-and-mouth disease(FMD),porcine reproductive and respiratory syndrome(PRRS),pseudorabie...[Objectives]This study was conducted to evaluate the immunization efficacy and infection status of classical swine fever(CSF),foot-and-mouth disease(FMD),porcine reproductive and respiratory syndrome(PRRS),pseudorabies(PR),and porcine circovirus type 2(PCV2)in large-scale pig farms.[Methods]Antibody and pathogen detection was performed on 56 serum samples collected in March 2025.[Results]The antibody qualification rates for CSF,FMD,and PRRS were 76.8%,73.2%,and 76.8%,respectively,all meeting the national standards.However,nursery pigs exhibited an immunity gap,indicating a need for timely booster vaccinations.No PRV gE antibodies or PCV2 antibodies were detected,reflecting the absence of vaccination against these diseases and suggesting significant effectiveness of comprehensive biosecurity measures.The low antibody qualification rate for PRRS in the nursery stage highlights the need for improved immunization management.[Conclusions]This study provides data support and practical insights for integrated disease prevention and control in large-scale pig farms.展开更多
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
文摘Antibody-mediated rejection(AMR)remains a leading cause of kidney allograft failure,posing significant clinical and economic challenges.Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss.The diagnostic criteria and classification of AMR have evolved considerably over the past three decades,driven largely by the Banff classification.The latest Banff 2022 classification introduced two additional subcategories of“microvascular inflammation,donor-specific antibody-negative,C4d-negative”and“probable AMR”.Traditionally,graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria,and the invasive biopsies.Noninvasive tools using blood and urine biomarkers,including cellular assays and molecular profiling,are increasingly being investigated.Technologies such as the Molecular Microscope Diagnostic System show promise,with studies reporting 80%sensitivity and 90%specificity in detecting AMR.Treatment of AMR remains inconsistent.Recent advances,including CD38 antibodies,have demonstrated up to 60%efficacy in reversing AMR,while complement inhibition shows potential in severe early cases.Ongoing clinical trials evaluating high-dose intravenous immunoglobulin,efgartigimod,fostamatinib,and other novel therapies aim to expand treatment options.These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.
文摘BACKGROUND This case report describes myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis with kidney involvement in a patient with relapsing polychondritis,which was successfully treated with Avacopan.Although relapsing polychondritis has been associated with anti-neutrophil cytoplasmic antibody-associated vasculitis,overlap can result in severe organ involvement,particularly renal damage progressing to end-stage kidney disease.This case presents a unique opportunity to evaluate the potential role of Avacopan as an alternative therapeutic option in managing myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis in the context of relapsing polychon-dritis highlighting a positive renal response despite treatment challenges.This is a case of a 69-year-old Caucasian woman who presented to our hospital’s emergency department with a 4 week history of inflammatory polychondritis affecting the auricular cartilage,accompanied by acute kidney injury.On admission,serum creatinine was elevated at 4.0 mg/dL,which progressively increased to 6.07 mg/dL on day 6.The renal biopsy revealed necrotizing and crescentic glomerulonephritis affecting more than 50%of the glomeruli.She was treated with a total of 2500 mg intravenous methylprednisolone over 3 days followed by oral prednisone.Induction treatment included intravenous cyclophosphamide induction,with plans for a total of 2 doses followed by transition to rituximab.However the patient was unable to tolerate rituximab due to allergic reaction so intravenous cyclophosphamide was continued for a total of 6 doses(cumulative dose 3000 mg).In the setting of persistent acute kidney injury,Avacopan was added to the regimen 3 months after diagnosis.Maintenance therapy included azathioprine in addition to Avacopan.Prednisone gradually tapered off at 6 months.CONCLUSION Avacopan may be beneficial in treating anti-neutrophil cytoplasmic antibody-associated vasculitis with coexisting relapsing polychondritis,especially in cases where preservation of kidney function is critical.Further research will be essential to validate these findings and refine treatment protocols for such complex cases.
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.
基金supported by the UCSI University under the Research Excellence and Innovation Grant(REIG)(grant numbers:REIG-FAS-2023/006,REIG-FAS-2024/001).
文摘Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.
文摘To determine how the auto-antibodies(Abs)profiles overlap in chronic hepatitis C infection(CHC)and autoimmune hepatitis(AIH)and correlate to liver disease.METHODSLevels of antinuclear Ab,smooth muscle antibody(SMA)and liver/kidney microsomal-1(LKM-1)Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection,20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG,alkaline phosphatase,total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies(auto-Abs)than CHC patients.Antinuclear Ab,SMA and LKM-1 Ab were also present in 36%of CHC patients and related to disease severity.CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG.These cases had longer disease duration compared with auto-Ab negative cases,but there was no difference in gender,age or viral load.KLM-1<sup>+</sup>Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH.Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage.Future studies will unravel any novel associations between these two diseases,whether genetic or other.
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.
基金supported by the Independent Research and Development Projects Foundation of Shanghai InnoStar Bio-Techology Co.,Ltd.(H23ZZYF01 and H24ZZYF01).
文摘Therapeutic antibodies are valued for their high specificity and selectivity in immu-notherapy.However,the potential toxicity they may elicit underscores the necessity of assessing their preclinical efficacy and safety using suitable animal models.In this context,we review the various categories and applications of humanized mice,which have been engrafted with human cells or tissues to mimic the human immune system.These models are extensively utilized in the nonclinical assessment and development of various antibody drugs,acting as a conduit to clinical research.However,several challenges remain,including the limited lifespan of humanized mice,inadequate en-graftment of human cells,and the rudimentary nature of the immune environment in these models.The development of humanized immune system models in mice pre-sents both opportunities and challenges,potentially leading to new insights into the evolution and application of antibody therapeutics.
基金supported by the Beijing Natural Science Foundation(Grant No.L244024)National Natural Science Foundation of China(Grant Nos.82172604 and 82473199)CSCO Clinical Oncology Research Foundation(Grant No.Y-2022HER2AZMS-0258).
文摘Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of patients with metastatic UC(mUC)remains poor(10-15%)2.
基金supported by the National Natural Science Foundation of China(No.12104396)the National Key R&D Program of China(Nos.2021YFF1200404 and 2021YFA1201200)+2 种基金the National Independent Innovation Demonstration Zone Shanghai Zhangjiang Major Projects(No.ZJZX2020014)the Starry Night Science Fund at Shanghai Institute for Advanced Study of Zhejiang University(No.SN-ZJU-SIAS-003)the Shanghai Artificial Intelligence Lab(No.P22KN00272),China.
文摘Antibodies currently comprise the predominant treatment modality for a variety of diseases;therefore,optimizing their properties rapidly and efficiently is an indispensable step in antibody-based drug development.Inspired by the great success of artificial intelligence-based algorithms,especially deep learning-based methods in the field of biology,various computational methods have been introduced into antibody optimization to reduce costs and increase the success rate of lead candidate generation and optimization.Herein,we briefly review recent progress in deep learning-based antibody optimization,focusing on the available datasets and algorithm input data types that are crucial for constructing appropriate deep learning models.Furthermore,we discuss the current challenges and potential solutions for the future development of general-purpose deep learning algorithms in antibody optimization.
基金supported by the National Natural Science Foundation of China(Nos.22304027 and 81570807)the Natural Science Foundation of Fujian Province(No.2022J01208)+2 种基金the Joint Funds for the Innovation of Science and Technology,Fujian Province(Nos.2024Y9109,2024Y9107,and 2024Y9103)the Startup Fund for Scientific Research,Fujian Medical University(No.XRCZX2021015)the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases,and Xiang An Biomedicine Laboratory(No.2023XAKJ0101018).
文摘Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.
文摘BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.
基金Supported by the National Natural Science Foundations of China(82271340,82071368)。
文摘Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrhagic stroke remains unknown.This study aimed to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and hemorrhagic stroke using the two-sample Mendelian randomization(MR)method.Comprehensive analyses were conducted using publicly available data from genome-wide association study(GWAS),which involved the whole genomes of 9724 European participants and 46 antibody measurement phenotypes,and summary statistics from the FinnGen dataset R12(including intracerebral hemorrhage and subarachnoid hemorrhage)were used.The causal relationship between the aforementioned immune responses and hemorrhagic stroke was analyzed using inverse-variance weighting,MR-Egger regression,weighted median,weighted mode,simple mode,and MR-pleiotropy residual sum and outlier(MR-PRESSO),while various sensitivity analyses were performed to assess heterogeneity and pleiotropy in the study findings.Results showed that human herpes virus 7(HHV-7)U14 antibody levels(OR:0.877,95%CI:0.797-0.964,P=0.007)exerted a protective effect against hemorrhagic stroke,and Chlamydia trachomatis(CT)tarp-D F2 antibody levels(OR:0.937,95%CI:0.885-0.992,P=0.025)had a potential protective effect;additionally,Epstein-Barr virus(EBV)ZEBRA antibody levels(OR:1.062,95%CI:1.012-1.114,P=0.014),human herpesvirus 6(HHV-6)p101k antibody levels(OR:1.054,95%CI:1.002-1.108,P=0.042),and cytomegalovirus(CMV)pp150 antibody levels(OR:1.086,95%CI:1.002-1.176,P=0.045)were potential risk factors for the disease.No significant pleiotropy or heterogeneity was observed in any of the MR analyses.Collectively,these findings confirmed a significant causal relationship between antibody-mediated immune responses and hemorrhagic stroke,and this study contributed to a deeper understanding of the potential mechanisms underlying hemorrhagic stroke onset.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81672638)。
文摘The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.
基金Supported by National Natural Science Foundation of China,No.81960115,No.82160123 and No.82260124Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University),Ministry of Education,No.GKEZZ202107+1 种基金Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,No.GKE-ZZ202218Guangxi Science and Technology Program,No.AD25069077.
文摘BACKGROUND Hepatitis B virus(HBV)infection is a leading cause of global hepatocellular carcinoma(HCC).Conventional biomarkers such as alpha-fetoprotein(AFP)demonstrate suboptimal sensitivity and specificity.Emerging evidence suggests that serum extra spindle pole bodies like 1(ESPL1)protein and p53 antibody may improve diagnostic accuracy.AIM To assess and compare the diagnostic performance of serum ESPL1 protein and p53 antibody in HBV-related HCC(HBV-HCC).METHODS This case-control study from the First Affiliated Hospital of Guangxi Medical University enrolled 30 patients with chronic hepatitis B(CHB),30 with HBV-related liver cirrhosis(HBV-LC),55 with HBV-HCC,and 30 healthy controls.Serum ESPL1 protein and p53 antibody levels were quantified via ELISA.Diagnostic performance was evaluated using receiver operating characteristic(ROC)curve analysis,including sensitivity,specificity,and correlation with AFP.RESULTS Serum ESPL1 protein levels progressively increased across disease stages(CHB:89.9 ng/L;HBV-LC:188.83 ng/L;HBV-HCC:317.63 ng/L),with a significantly higher area under the ROC curve(AUC=0.917)than either p53 antibody(AUC=0.725)or AFP(AUC=0.678).p53 antibody levels were significantly elevated only in the HBVHCC group.ESPL1 demonstrated superior sensitivity and concordance with histopathological findings.A significant correlation between ESPL1 and p53 antibody levels was observed exclusively in the HBV-HCC group(r=0.320,P=0.017),suggesting potential interplay in malignant transformation.CONCLUSION Serum ESPL1 protein,a promising biomarker for early HBV-HCC detection,outperforms p53 antibody in diagnostic reliability.Higher ESPL1 levels correlate with increased HCC risk in chronic HBV patients.
文摘DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).
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).
文摘Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.
基金Supported by Guizhou Provincial Department of Agriculture and Rural Affairs Project(QNYZZZ[2017]No.12,GZSZCYJSTX-04)2025 Quality Supervision and Sampling Project of Normal Temperature Semen for Breeding Pigs(2025-1-10).
文摘[Objectives]This study was conducted to evaluate the immunization efficacy and infection status of classical swine fever(CSF),foot-and-mouth disease(FMD),porcine reproductive and respiratory syndrome(PRRS),pseudorabies(PR),and porcine circovirus type 2(PCV2)in large-scale pig farms.[Methods]Antibody and pathogen detection was performed on 56 serum samples collected in March 2025.[Results]The antibody qualification rates for CSF,FMD,and PRRS were 76.8%,73.2%,and 76.8%,respectively,all meeting the national standards.However,nursery pigs exhibited an immunity gap,indicating a need for timely booster vaccinations.No PRV gE antibodies or PCV2 antibodies were detected,reflecting the absence of vaccination against these diseases and suggesting significant effectiveness of comprehensive biosecurity measures.The low antibody qualification rate for PRRS in the nursery stage highlights the need for improved immunization management.[Conclusions]This study provides data support and practical insights for integrated disease prevention and control in large-scale pig farms.
