2024
Cathepsin B Nuclear Flux in a DNA-Guided “Antinuclear Missile” Cancer Therapy
Cao F, Tang C, Chen X, Tu Z, Jin Y, Turk O, Nishimura R, Ebens A, Dubljevic V, Campbell J, Zhou J, Hansen J. Cathepsin B Nuclear Flux in a DNA-Guided “Antinuclear Missile” Cancer Therapy. ACS Central Science 2024, 10: 1562-1572. PMID: 39220699, PMCID: PMC11363321, DOI: 10.1021/acscentsci.4c00559.Peer-Reviewed Original ResearchAntinuclear antibodiesCancer therapyTumor-specific surface antigenLysosomal protease cathepsin BAntibody-drug conjugatesNecrotic tumorTumor environmentExtracellular nucleic acidsSurface antigensProtease cathepsin BCancer cellsTumorNucleoside salvage pathwayDrug linkersNucleoside salvageTherapyCross membrane barriersMembrane barrierCathepsin BLiving cancer cellsDNA guidesAntinuclearSalvage pathwayCathepsinNuclear penetration
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
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
2017
Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids
Johnson CH, Santidrian AF, LeBoeuf SE, Kurczy ME, Rattray NJW, Rattray Z, Warth B, Ritland M, Hoang LT, Loriot C, Higa J, Hansen JE, Felding BH, Siuzdak G. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids. Cancer & Metabolism 2017, 5: 9. PMID: 29093815, PMCID: PMC5663111, DOI: 10.1186/s40170-017-0171-2.Peer-Reviewed Original ResearchLung metastasesMFP tumorsMammary fat pad tumorsCholesterol sulfateCancer cellsPrimary mammary fat pad tumorSpontaneous tumor metastasisMouse xenograft modelPathway analysisDistant organ sitesPrimary cancerNormal lungMouse modelXenograft modelOrgan sitesMetastasisMetastatic nicheDNA/RNA synthesisTumor cellsCancer metastasisNormal tissuesTumor metastasisTumorsDistant sitesMetabolic characteristics
2015
DNA-dependent targeting of cell nuclei by a lupus autoantibody
Weisbart RH, Chan G, Jordaan G, Noble PW, Liu Y, Glazer PM, Nishimura RN, Hansen JE. DNA-dependent targeting of cell nuclei by a lupus autoantibody. Scientific Reports 2015, 5: 12022. PMID: 26156563, PMCID: PMC4496662, DOI: 10.1038/srep12022.Peer-Reviewed Original ResearchConceptsLupus anti-DNA autoantibodiesAnti-DNA autoantibodiesTumor cell nucleiSingle-chain variable fragmentPotential therapeutic applicationsLupus autoantibodiesTherapeutic approachesIschemic conditionsCertain cancer cellsChain variable fragmentCancer cellsCell nucleiAutoantibodiesNecrotic regionsVariable fragmentTherapeutic applicationsDNA damageNuclear uptakeScFvMalignancyGreater understandingTumorsStrokeDiseaseOptimizing a Lupus Autoantibody for Targeted Cancer Therapy
Noble PW, Chan G, Young MR, Weisbart RH, Hansen JE. Optimizing a Lupus Autoantibody for Targeted Cancer Therapy. Cancer Research 2015, 75: 2285-2291. PMID: 25832653, DOI: 10.1158/0008-5472.can-14-2278.Peer-Reviewed Original Research
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 role
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
2007
Antibody-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
2004
Antibody-mediated transduction of p53 selectively kills cancer cells.
Weisbart RH, Hansen JE, Chan G, Wakelin R, Chang SS, Heinze E, Miller CW, Koeffler PH, Yang F, Cole GM, Min YS, Nishimura RN. Antibody-mediated transduction of p53 selectively kills cancer cells. International Journal Of Oncology 2004, 25: 1867-73. PMID: 15547728, DOI: 10.3892/ijo.25.6.1867.Peer-Reviewed Original ResearchConceptsCancer cellsWild-type p53Expression of MDM2Cancer cell linesTransduction of p53Potential efficacyCertain cancersNon-specific toxicityFunctional defectsHuman cancersP53Cell linesCancerResult of mutationsGene therapyPrimary cellsViral vectorsCellsVivoNuclear exclusionTherapyFusion proteinFv fragmentProtein transductionAntibodies