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
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
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
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
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
Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which...Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.展开更多
In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care ...In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.展开更多
BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies ma...BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies may play an important role in this process,but cases of AM with positive anti-SSA/Ro antibodies are rare.In addition,arrhythmias,such as atrioventricular block,are very common in patients with autoimmune diseases,but severe atrioventricular block requiring permanent pacemaker implantation is extremely rare.CASE SUMMARY The patient in this case had AM with anti-SSA/Ro antibody positivity,which was associated with connective tissue disease,and the patient subsequently developed CAVB.After intensive immunosuppressive therapy,the antibody test results became negative,and pulmonary hypertension significantly improved.However,the outcome of permanent pacemaker implantation did not change.CONCLUSION In clinical practice,the awareness of adult AM associated with autoimmune diseases combined with CAVB should be strengthened in clinicians,and anti-SSA/Ro antibodies may play a role in this process.Therefore,improving the detection of antibodies and early intervention,such as active immunosuppression therapy,may be very important for improving disease prognosis.For patients who do not respond to immunosuppressive therapy,implantation of a permanent pacemaker may become an essential treatment option.展开更多
BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-Eu...BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.展开更多
Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This stud...Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.展开更多
Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.Method A total of 10,215 s...Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA).Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively).Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.展开更多
Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ...The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.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
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
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.
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.
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 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).
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.
文摘Antibody-mediated rejection(AMR)represents a major challenge in kidney transplantation,significantly contributing to tissue injury and graft failure.AMR is primarily driven by donor-specific alloantibodies(DSAs),which recognize and bind to specific target antigens present within the transplanted kidney tissue.Upon binding,these DSAs commonly initiate activation of the complement system within the graft.The activation of the complement cascade sets off a powerful inflammatory response characterized by the recruitment and activation of immune cells,endothelial damage,and subsequent tissue injury.This inflammation underlies many clinical and histological manifestations of AMR,making complement activation a critical player in the disease process.Advancements in our understanding of how complement pathways contribute to kidney graft injury have opened new avenues for therapeutic intervention.Recent research has facilitated the development and application of novel therapies specifically designed to inhibit complement activation.Such targeted complement-inhibitory strategies have shown promise in improving graft outcomes by inhibiting complement-mediated damage and extending graft survival.This review comprehensively discusses the critical role of complement activation in inducing kidney graft injury with a focus on its role in AMR.By elucidating the detailed mechanisms and contributions of complement pathways,the review seeks to enhance the understanding necessary for developing targeted therapeutic interventions to prevent or treat AMR effectively.
文摘In this manuscript, we present a case report of a child with 16-year-old previously healthy Hispanic male who presented for progressive proximal muscle weakness, rash, and dysphagia. He was admitted to the acute care floor and diagnosed with juvenile dermatomyositis and found to be positive for anti-Mi-2 alpha, anti-Mi-2 beta, and anti-MDA-5 antibodies. He gradually improved with a combination of steroid, immunomodulatory treatment, and physical therapy. This case outlines the clinical course of a patient with this rare disorder as well as the importance of understanding the role of associated antibodies to manage potential long-term sequelae.
文摘BACKGROUND Autoimmune myocarditis(AM)associated with autoimmune diseases can cause complete atrioventricular block(CAVB),but the related autoantigens and the underlying mechanisms are unclear.Anti-SSA/Ro antibodies may play an important role in this process,but cases of AM with positive anti-SSA/Ro antibodies are rare.In addition,arrhythmias,such as atrioventricular block,are very common in patients with autoimmune diseases,but severe atrioventricular block requiring permanent pacemaker implantation is extremely rare.CASE SUMMARY The patient in this case had AM with anti-SSA/Ro antibody positivity,which was associated with connective tissue disease,and the patient subsequently developed CAVB.After intensive immunosuppressive therapy,the antibody test results became negative,and pulmonary hypertension significantly improved.However,the outcome of permanent pacemaker implantation did not change.CONCLUSION In clinical practice,the awareness of adult AM associated with autoimmune diseases combined with CAVB should be strengthened in clinicians,and anti-SSA/Ro antibodies may play a role in this process.Therefore,improving the detection of antibodies and early intervention,such as active immunosuppression therapy,may be very important for improving disease prognosis.For patients who do not respond to immunosuppressive therapy,implantation of a permanent pacemaker may become an essential treatment option.
基金Supported by Ministry of Science and Technology,Taiwan,No.MOST 111-2314-B-002-226National Taiwan University Hospital,Hsin-Chu Branch,No.112-BIH017The Liver Disease Prevention and Treatment Research Foundation,Taiwan.
文摘BACKGROUND Anti-drug antibodies(ADAs)can reduce the effectiveness of biologics.While human leukocyte antigen(HLA)-DQA1*05 allele is linked to ADA formation in European Crohn’s disease patients,its relevance in non-European populations remains unclear.AIM To investigate HLA genotypes associated with the development of ADAs in Taiwan Region of China inflammatory bowel disease(IBD)patients treated with biologics.METHODS In this multicenter study,IBD patients treated with anti-tumor necrosis factor(TNF),anti-integrin,or anti-interleukin(IL)-12/23 therapies from April 2022 to June 2024 were enrolled.All participants underwent next-generation sequencing for HLA genotyping.ADA levels were measured via enzyme linked immunosorbent assay.HLA allele frequencies were compared between ADA-positive and ADA-negative groups,and against general Taiwan Region of China population data.RESULTS Ninety-five IBD patients were included:58 received anti-TNF therapy(38 infliximab,20 adalimumab),27 antiintegrin,and 10 anti-IL-12/23.ADAs occurred only in the anti-TNF group(n=22):19 infliximab(50%)and 3 adalimumab(15%).No ADAs developed in patients on anti-integrin or anti-IL-12/23 agents.HLA-C*03:04:01 was significantly associated with anti-infliximab ADAs(31.6%vs 0%,P=0.02),and HLA-B*15:18:01 with anti-adalimumab ADAs(66.7%vs 0%,P=0.016).HLA-DQA1*05 was not associated with ADA formation.Frequencies of HLA-C*03:04:01(8.4%vs 10.5%)and HLA-B*15:18:01(1.6%vs 0.6%)in IBD patients were comparable to those in the general population.ADA titers were inversely correlated with serum drug levels.CONCLUSION In Taiwan Region of China IBD patients,HLA-C*03:04:01 and HLA-B*15:18:01 were significantly associated with ADA development to infliximab and adalimumab,respectively.HLA-DQA1*05 was not predictive,highlighting ethnic differences in genetic predisposition to immunogenicity.
基金supported by the National Key Research and Development Program of China[2018YFB0407200]National Natural Science Foundation of China[61975239]Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences[2019-I2M-5061].
文摘Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.
基金approved by the Ethics Committee of the Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention(GXIRB 2018-0005),and the participants signed informed consent forms.
文摘Objective Pertussis cases have increased markedly since 2018 in Guangxi.The aim of this study was to evaluate antibody levels and the infection status of pertussis in the resident population.Method A total of 10,215 serum samples from residents were collected from August-November 2018 and tested for anti-pertussis IgG and toxin IgG using the enzyme-linked immunosorbent assay(ELISA).Results Of the collected samples,1,833(17.94%)tested positive for anti-pertussis IgG,with the median concentration of 16.06 IU/mL.Antibody level<10 IU/mL accounted for more than 60%in children under 4 years of age,but declined with age,whereas the percentages of the other three levels(10-40,40-50,and≥50 IU/mL)increased almost with age(P<0.001).Moreover,7,924 samples were selected for anti-pertussis toxin IgG,of which 653(8.24%)tested positive(≥40 IU/mL)with the median concentration of 5.89 IU/mL,and 204 participants(2.56%)had recent pertussis infection(≥100 IU/mL).Among the different age groups,the highest rates of positivity and recent infection were observed at 11-20 years of age,the lowest positivity rate at 5 years of age,and the lowest recent infection rate at 4 years of age(P<0.001,P=0.005,respectively).Conclusion The survey results showed that all age groups in Guangxi lacked immunity against pertussis,which was one of the main factors contributing to the resurgence of pertussis in 2018.In addition,the prevalence of pertussis is relatively high in Guangxi,and its incidence is seriously underestimated,especially in adolescents and adults.
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.
文摘The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.
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the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
