2022
Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody
Chen X, Cuffari BJ, Dubljevic V, Shirali A, Zhou J, Campbell JA, Suits SC, O'Sullivan KM, Hansen JE. Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody. ImmunoHorizons 2022, 6: 356-365. PMID: 35697479, DOI: 10.4049/immunohorizons.2100091.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trapsAnti-DNA autoantibodiesRelease of NETsInhibition of NETosisOncology clinical trialsDifferentiated PLB-985 cellsMechanisms of NETosisCalcium ionophore ionomycinPLB-985 cellsIndependent NETosisC57BL/6 miceClinical trialsExtracellular trapsSuch AbsAutoantibodiesNeutrophil biologyDNA damage responseTherapeutic potentialNETosisHistone citrullinationIonophore ionomycinWestern blotSignificant inhibitionMultiple diseasesNeutrophils
2021
ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transporters
2020
LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy
Chen Y, Jiang T, Zhang H, Gou X, Han C, Wang J, Chen AT, Ma J, Liu J, Chen Z, Jing X, Lei H, Wang Z, Bao Y, Baqri M, Zhu Y, Bindra RS, Hansen JE, Dou J, Huang C, Zhou J. LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy. Nature Cell Biology 2020, 22: 1276-1285. PMID: 33005030, PMCID: PMC7962994, DOI: 10.1038/s41556-020-00586-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBrain NeoplasmsBreast NeoplasmsCell ProliferationDNA DamageDNA RepairFemaleGamma RaysHumansMiceMice, Inbred BALB CMice, NudeMutS Homolog 2 ProteinNuclear ProteinsPhosphorylationRadiation-Sensitizing AgentsSignal TransductionTumor Cells, CulturedXenograft Model Antitumor Assays
2018
Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications
Rattray Z, Dubljevic V, Rattray NJW, Greenwood DL, Johnson CH, Campbell JA, Hansen JE. Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications. Biochemical And Biophysical Research Communications 2018, 496: 858-864. PMID: 29374508, DOI: 10.1016/j.bbrc.2018.01.139.Peer-Reviewed Original Research
2016
A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
Chen Z, Patel JM, Noble PW, Garcia C, Hong Z, Hansen JE, Zhou J. A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors. Oncotarget 2016, 7: 59965-59975. PMID: 27494868, PMCID: PMC5312362, DOI: 10.18632/oncotarget.11015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntibodies, CatalyticBreast NeoplasmsCell Line, TumorDNADoxorubicinDrug Delivery SystemsFemaleHumansLactic AcidLupus Coagulation InhibitorMammary Neoplasms, AnimalMiceMice, Inbred BALB CNanoparticlesPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerTumor MicroenvironmentConceptsDelivery of nanoparticlesDOX-loaded nanoparticlesTumor-targeting mechanismDrug delivery mechanismsAmount of moleculesNanoparticle deliveryLupus anti-DNA autoantibodiesNanoparticlesProof of conceptRelease of DNASurface modificationBind moleculesAutocatalytic effectDelivery mechanismTumor neovasculatureMoleculesDeliveryDoxorubicinTumor microenviromentMajor limitationEfficiencyLigandsSubsequent treatmentToxic agentsDNA
2014
A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells
Noble PW, Young MR, Bernatsky S, Weisbart RH, Hansen JE. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells. Scientific Reports 2014, 4: 5958. PMID: 25091037, PMCID: PMC5380011, DOI: 10.1038/srep05958.Peer-Reviewed Original ResearchConceptsLupus autoantibodiesTherapeutic agentsCancer cellsSystemic lupus erythematosusBRCA2-deficient cellsLupus erythematosusBRCA2-deficient cancer cellsDLD1 colon cancer cellsColon cancer cellsSuch antibodiesLower riskAutoantibodiesSpecific cancersAntibodiesMalignancyDifferential effectsToxic effectsPotential utilityCellsAgentsFurther supportDNA-damaging agentsErythematosusTherapyCancer
2012
Targeting Cancer with a Lupus Autoantibody
Hansen JE, Chan G, Liu Y, Hegan DC, Dalal S, Dray E, Kwon Y, Xu Y, Xu X, Peterson-Roth E, Geiger E, Liu Y, Gera J, Sweasy JB, Sung P, Rockwell S, Nishimura RN, Weisbart RH, Glazer PM. Targeting Cancer with a Lupus Autoantibody. Science Translational Medicine 2012, 4: 157ra142. PMID: 23100628, PMCID: PMC3713477, DOI: 10.1126/scitranslmed.3004385.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAnti-DNA antibodiesLupus autoantibodiesProstate cancerCancer therapyLupus anti-DNA antibodiesHuman tumor xenograftsDNA-damaging therapiesCultured tumor cellsSLE patientsLupus erythematosusSLE pathophysiologyAutoimmune diseasesDose doxorubicinTumor xenograftsAutoantibodiesHuman cancer cellsTherapyTherapeutic agentsTumor cellsCancerCancer cellsLupusMalignancyPrecise roleA Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets
Weisbart RH, Gera JF, Chan G, Hansen JE, Li E, Cloninger C, Levine AJ, Nishimura RN. A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets. Molecular Cancer Therapeutics 2012, 11: 2169-2173. PMID: 22863609, DOI: 10.1158/1535-7163.mct-12-0476-t.Peer-Reviewed Original ResearchConceptsBispecific antibodiesBispecific single-chain Fv fragmentsMonoclonal antibody 3G5Cancer therapyDelivery of antibodiesIntracellular targetsMolecular therapyTherapeutic useTherapeutic regulationMonoclonal antibodiesTherapyAntibodiesMAb 3E10Single-chain Fv fragmentInhibits growthP53 levelsImportant targetMDM2Limited accessFv fragmentTargetTumors
2010
Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats
Zhan X, Ander BP, Liao IH, Hansen JE, Kim C, Clements D, Weisbart RH, Nishimura RN, Sharp FR. Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats. Stroke 2010, 41: 538-543. PMID: 20075343, PMCID: PMC2957177, DOI: 10.1161/strokeaha.109.572537.Peer-Reviewed Original ResearchConceptsFocal cerebral ischemiaCerebral ischemiaInfarction volumeSensorimotor functionSaline-treated control groupIntraluminal suture techniqueExperimental ischemic strokeExperimental stroke modelsMiddle cerebral arteryOnset of ischemiaInfarct volumeIschemic brainIschemic strokeCerebral arteryFocal ischemiaControl brainsStroke modelTail veinIschemiaControl groupSuture techniqueWestern blotEndogenous Hsp70RatsBrain
2009
Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo.
Heinze E, Baldwin S, Chan G, Hansen J, Song J, Clements D, Aragon R, Nishimura R, Reeves M, Weisbart R. Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo. International Journal Of Oncology 2009, 35: 167-73. PMID: 19513564, DOI: 10.3892/ijo_00000325.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalApoptosisBreast NeoplasmsCaspase 3Cell Line, TumorCell SurvivalColorectal NeoplasmsDose-Response Relationship, DrugFemaleForkhead Transcription FactorsHumansImmunoconjugatesImmunoglobulin FragmentsLiver NeoplasmsMiceMice, Inbred BALB COvarian NeoplasmsRecombinant Fusion ProteinsTransfectionConceptsColon cancer metastasisCancer cellsCancer metastasisColon cancer cellsBALB/c miceProtein therapyImmune suppressive functionCell deathDose-dependent cell deathRegulatory cellsTumor burdenClinical efficacySyngeneic modelC miceNuclear transcription factorMouse modelSuppressive functionInhibits metastasisMetastasisZ-VAD-FMKClinical potentialTherapyCaspase-3Foxp3Cell killing
2008
p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*
Ma QL, Yang F, Calon F, Ubeda OJ, Hansen JE, Weisbart RH, Beech W, Frautschy SA, Cole GM. p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*. Journal Of Biological Chemistry 2008, 283: 14132-14143. PMID: 18347024, PMCID: PMC2376243, DOI: 10.1074/jbc.m708034200.Peer-Reviewed Original ResearchConceptsCultured hippocampal neuronsAlzheimer's diseaseHippocampal neuronsDendritic spinesTransgenic miceAlzheimer's disease brainAlzheimer's amyloid pathologyAlzheimer's disease (AD) pathogenesisBeta-amyloid oligomersOligomer treatmentSrc family tyrosine kinase inhibitor PP2P-NR2BSynaptic deficitsAmyloid pathologyDisease brainTyrosine kinase inhibitor PP2Disease pathogenesisCognitive deficitsMental retardation syndromeProtein drebrinKinase inhibitor PP2DiseaseNeuronsRetardation syndromeMice
2007
Intranuclear Protein Transduction through a Nucleoside Salvage Pathway*
Hansen JE, Tse CM, Chan G, Heinze ER, Nishimura RN, Weisbart RH. Intranuclear Protein Transduction through a Nucleoside Salvage Pathway*. Journal Of Biological Chemistry 2007, 282: 20790-20793. PMID: 17525162, DOI: 10.1074/jbc.c700090200.Peer-Reviewed Original ResearchConceptsNucleoside salvage pathwaySalvage pathwaySpecific nuclear localizationCargo proteinsGene regulationMolecular delivery vehiclesProtein transportProtein transductionTranscription factorsNuclear localizationGene expressionNuclear membraneHuman diseasesLiving cellsCell nucleiCell membraneNew molecular therapiesNumerous diseasesPathwayTransductionCellsRegulationMolecular therapyFirst demonstrationNew avenuesAntibody-Mediated p53 Protein Therapy Prevents Liver Metastasis In vivo
Hansen JE, Fischer LK, Chan G, Chang SS, Baldwin SW, Aragon RJ, Carter JJ, Lilly M, Nishimura RN, Weisbart RH, Reeves ME. Antibody-Mediated p53 Protein Therapy Prevents Liver Metastasis In vivo. Cancer Research 2007, 67: 1769-1774. PMID: 17308119, DOI: 10.1158/0008-5472.can-06-3783.Peer-Reviewed Original ResearchConceptsLiver metastasesMetastasis ScoreBALB/c miceCancer metastasisCancer cellsMediator of intracellularColon cancer metastasisProtein therapySplenic injectionClinical efficacyControl miceDelivery of p53Significant clinical potentialC micePortal veinColon cancer cellsImmunohistochemical stainingMouse modelSecond injectionMetastasisClinical potentialMiceTherapyVivoP53
2006
Antibody-mediated Hsp70 protein therapy
Hansen JE, Sohn W, Kim C, Chang SS, Huang NC, Santos DG, Chan G, Weisbart RH, Nishimura RN. Antibody-mediated Hsp70 protein therapy. Brain Research 2006, 1088: 187-196. PMID: 16630585, DOI: 10.1016/j.brainres.2006.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBlotting, WesternCell SurvivalCells, CulturedCerebral CortexChlorocebus aethiopsDose-Response Relationship, DrugHSP70 Heat-Shock ProteinsHumansHydrogen PeroxideImmunoglobulin Variable RegionNeuronsOxidantsProtein TransportRatsRats, WistarRecombinant Fusion ProteinsTransduction, GeneticTransfectionConceptsPrimary rat cortical neuronsRat cortical neuronsCortical neuronsIntracellular HSP70 levelsCOS-7 cellsSingle-chain Fv fragmentAnti-DNA antibodiesProtein therapyIntracellular HSP70Stressful stimuliFv fragmentMAb 3E10Hsp70 levelsNeuronsTherapyProtein transduction domainSubsequent exposureCellsHuman diseasesNovel protein transduction domainFirst evidenceTransduction domainLiving cellsHSP70Fusion proteinRole of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease
Zhao L, Ma QL, Calon F, Harris-White ME, Yang F, Lim GP, Morihara T, Ubeda OJ, Ambegaokar S, Hansen JE, Weisbart RH, Teter B, Frautschy SA, Cole GM. Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease. Nature Neuroscience 2006, 9: 234-242. PMID: 16415866, DOI: 10.1038/nn1630.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseCognitive deficitsDrebrin lossMental retardationP21-activated kinase pathwaysTransgenic mouse modelDendritic spine morphogenesisPotential causal roleP21-activated kinaseHippocampal neuronsDendritic spinesMouse modelΒ-amyloidAdult miceMemory impairmentDiseaseProtein drebrinSpine morphogenesisCausal roleCofilin pathologyDeficitsPAK pathwayPathologyPAK inhibitionKinase pathway
2005
Antibody Mediated Transduction of Therapeutic Proteins into Living Cells
Hansen JE, Weisbart RH, Nishimura RN. Antibody Mediated Transduction of Therapeutic Proteins into Living Cells. The Scientific World JOURNAL 2005, 5: 782-788. PMID: 16170440, PMCID: PMC5936519, DOI: 10.1100/tsw.2005.98.Commentaries, Editorials and LettersMeSH KeywordsAnimalsAutoantibodiesBiological Transport, ActiveCells, CulturedDrug Delivery SystemsEndocytosisGene Products, tatHIV-1HumansImmunoglobulin FragmentsLymphokinesMicePeptide FragmentsProtein TransportProteinsSialoglycoproteinsSignal TransductionTat Gene Products, Human Immunodeficiency VirusConceptsProtein transduction domainTransduction domainNovel protein transduction domainTherapeutic proteinsReceptor-mediated endocytosisSuch proteinsHIV-1 Tat proteinCell-penetrating peptidesMAb 3E10Active proteinLiving cellsCell membraneProteinTat proteinProtein therapyCellsSingle-chain fragmentTherapeutic peptidesRecent studiesFv fragmentDomainFragmentsDirect deliveryEndocytosisTransductionAn intracellular delivery vehicle for protein transduction of micro-dystrophin
Weisbart RH, Hansen JE, Nishimura RN, Chan G, Wakelin R, Chang SS, Baresi L, Chamberlain JS. An intracellular delivery vehicle for protein transduction of micro-dystrophin. Journal Of Drug Targeting 2005, 13: 81-87. PMID: 15823959, DOI: 10.1080/10611860400029002.Peer-Reviewed Original Research