2015
Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Auletta J, Eid S, Wuttisarnwattana P, Silva I, Metheny L, Keller M, Guardia‐Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga L, Ganguly S, Tyler M, Wilson D, Cooke K. Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation. Stem Cells 2015, 33: 601-614. PMID: 25336340, PMCID: PMC4304927, DOI: 10.1002/stem.1867.Peer-Reviewed Original ResearchConceptsT cell expansionT cell proliferationGraft-VersusHost diseaseLeukemia activityExperimental allogeneic bone marrow transplantationDonor T cell expansionAllogeneic bone marrow transplantationCytotoxic T cell activityAlloreactive T cell proliferationPotent GVL effectCyclo-oxygenase inhibitionT cell activityT cell suppressionBone marrow transplantationMarrow-derived mesenchymal stromal cellsSecondary lymphoid organsSplenic T cellsSplenic marginal zoneMixed leukocyte cultureMesenchymal stromal cellsBMT miceEP2 agonismGVL activityGVL effect
2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice
Haarberg K, Li J, Heinrichs J, Wang D, Liu C, Bronk C, Kaosaard K, Owyang A, Holland S, Masuda E, Tso K, Blazar B, Anasetti C, Beg A, Yu X. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 2013, 122: 2500-2511. PMID: 23908466, PMCID: PMC3790515, DOI: 10.1182/blood-2012-12-471938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SeparationDisease Models, AnimalEnzyme InhibitorsFlow CytometryGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationIsoenzymesLeukemiaLymphocyte ActivationLymphomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C-alphaProtein Kinase C-thetaT-LymphocytesConceptsHematopoietic cell transplantationDonor T cell proliferationAllogeneic hematopoietic cell transplantationT cell proliferationGVL activityGVL effectCytokine productionT cellsPharmacologic inhibitionChemokine/cytokine productionT-cell cytotoxicDonor T cellsPreclinical murine modelsPotential therapeutic targetT cell activationGVHD inductionGVHD preventionPrevents GVHDHost diseaseLeukemia effectSevere graftTherapeutic optionsCell transplantationEffective therapyPharmacologic approaches
2011
Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu X. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 2011, 118: 5011-5020. PMID: 21856864, PMCID: PMC3208306, DOI: 10.1182/blood-2011-03-340315.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCells, CulturedCombined Modality TherapyGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationLeukemiaMiceMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNuclear Receptor Subfamily 1, Group F, Member 3T-Box Domain ProteinsTh1 CellsTh17 CellsTransplantation, HomologousConceptsHematopoietic cell transplantationGVL effectT-betT cellsTranscription factor T-betPrevention of GVHDDonor T cellsCD8 T cellsAmeliorated GVHDGVL activityNaive ThTh17 subsetAdoptive transferCell transplantationTh17 differentiationEffective therapyHematologic malignanciesAllogeneic hostsGVHDMajor MHCTh1Regulatory phenotypeSkewed differentiationTargeted disruptionRORγt
2007
Benzodiazepine-423, an Inhibitor of Mitochondrial Respiration, Causes Selective Apoptosis of Activated Lymphocytes and Reverses Experimental GVHD While Preserving GVL Effects.
Gatza E, Clouthier S, Reddy P, Liu C, Opipari A, Glick G, Ferrara J. Benzodiazepine-423, an Inhibitor of Mitochondrial Respiration, Causes Selective Apoptosis of Activated Lymphocytes and Reverses Experimental GVHD While Preserving GVL Effects. Blood 2007, 110: 68. DOI: 10.1182/blood.v110.11.68.68.Peer-Reviewed Original ResearchT cellsGVL effectExperimental GVHDDonor CD4T cell-mediated modelBeneficial GVL effectComplete donor engraftmentDay of BMTEvidence of lymphomaSpleen T cellsEL-4 lymphomaEL-4 lymphoma cellsMitochondrial membrane potentialSelective apoptosisB6 recipientsGVHD inductionSyngeneic BMTAllogeneic BMTHost diseaseDonor engraftmentAllogeneic recipientsImproved survivalClinical scoresMitochondrial respirationMembrane potentialβ2 integrins separate graft-versus-host disease and graft-versus-leukemia effects
Liang Y, Liu C, Djeu J, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, Yu X. β2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 2007, 111: 954-962. PMID: 17928532, PMCID: PMC2200850, DOI: 10.1182/blood-2007-05-089573.Peer-Reviewed Original ResearchConceptsT cellsHost diseaseLeukemia effectMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelWild-type donor T cellsAllogeneic hematopoietic stem cell transplantationDonor T-cell infiltrationDonor-derived T cellsHematopoietic stem cell transplantationBeta2 integrinsAnalysis of alloreactivityLess GVHD morbidityDevelopment of GVHDDonor T cellsGVHD target organsT cell infiltrationBone marrow transplantation modelStem cell transplantationWT T cellsT cell activationGVHD morbidityGVL activityGVL effectLess GVHD
2005
Critical Role for CCR1:CCL5 (RANTES) Receptor Ligand Interactions in Modulating Allogeneic T Cell Responses Following Bone Marrow Transplantation.
Choi S, Hildebrandt G, Silva I, Olkiewicz K, Chensue S, Liu C, Chaudhary M, Fisher J, Lane T, Cooke K. Critical Role for CCR1:CCL5 (RANTES) Receptor Ligand Interactions in Modulating Allogeneic T Cell Responses Following Bone Marrow Transplantation. Blood 2005, 106: 3107. DOI: 10.1182/blood.v106.11.3107.3107.Peer-Reviewed Original ResearchT cell responsesGVL effectAllo-SCTT cellsCell responsesChemokine receptorsAllogeneic T-cell responsesAllo-SCT recipientsDonor T-cell alloreactivityGVHD target tissuesSerum IFNγ levelsSeverity of GVHDTarget tissuesLeukemia-free survivalClinical scoring systemBone marrow transplantationT cell expansionT-cell alloreactivityBone marrow inoculumHost target tissuesActivated T cellsP815 tumor cellsDose-dependent mannerHigher tumor dosesAcute graft
2004
Allo-Antigen Expression on Both APCS and Tumor Is Required To Elicit an Effective GVL Response after Experimental Allogeneic BMT.
Reddy P, Maeda Y, Liu C, Dinarello C, Ferrara J. Allo-Antigen Expression on Both APCS and Tumor Is Required To Elicit an Effective GVL Response after Experimental Allogeneic BMT. Blood 2004, 104: 595. DOI: 10.1182/blood.v104.11.595.595.Peer-Reviewed Original ResearchDonor T cellsAntigen presenting cellsT cellsAllogeneic BMTHost antigen presenting cellsLeukemia/tumor effectClass ITarget tissuesComplete donor chimerismBone marrow chimerasMinor H antigensPro-inflammatory cytokinesMalignant target cellsMHC class ICytokine blockadeGVL effectTCD BMGVH reactionGVL responseHistologic presenceDonor chimerismTumor effectSecond tumorImmunotherapeutic potentialSyngeneic controlsCCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT.
Hildebrandt G, Choi S, Olkiewicz K, Chensue S, Liu C, Cooke K. CCR1 Expression on Donor Leukocytes Is Critical to the Development of Graft Versus Host Disease after Allogeneic SCT. Blood 2004, 104: 3067. DOI: 10.1182/blood.v104.11.3067.3067.Peer-Reviewed Original ResearchT cell responsesAllo-SCTCCR1 expressionDonor leukocytesHost diseaseT cellsCell responsesDonor T-cell responsesGraft Versus Host DiseaseAllogeneic stem cell transplantationSerum IFNγ levelsTranslocation of endotoxinVersus Host DiseaseDonor T cellsSeverity of GVHDDonor cellsClinical scoring systemStem cell transplantationT cell expansionAcute graftGVL effectSignificant GVHDTNFa levelsAllogeneic SCTClinical GVHDHistone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect
Reddy P, Maeda Y, Hotary K, Liu C, Reznikov L, Dinarello C, Ferrara J. Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3921-3926. PMID: 15001702, PMCID: PMC374345, DOI: 10.1073/pnas.0400380101.Peer-Reviewed Original ResearchConceptsBone marrow transplantationSuberoylanilide hydroxamic acidAdministration of SAHAProinflammatory cytokinesGVL activityAcute graftHost diseaseHost antigensTime of BMTAllogeneic bone marrow transplantationDonor/recipient combinationsEffects of SAHACytotoxic T cell responsesCytotoxic responseBeneficial GVL effectLeukemia-free survivalT cell proliferativeHistone deacetylase inhibitor suberoylanilide hydroxamic acidT cell responsesVehicle-treated animalsGastrointestinal tract integrityInhibitor suberoylanilide hydroxamic acidHistone deacetylase inhibitionAcute GVHDGVL effect
2003
Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect
Clouthier S, Cooke K, Teshima T, Lowler K, Liu C, Connolly K, Ferrara J. Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect. Transplantation And Cellular Therapy 2003, 9: 592-603. PMID: 14506661, DOI: 10.1016/s1083-8791(03)00230-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCD4 Lymphocyte CountCD8-Positive T-LymphocytesCell DivisionCell Line, TumorDisease Models, AnimalFemaleFibroblast Growth Factor 10Fibroblast Growth FactorsGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-2IntestinesLipopolysaccharidesLiverLymphocyte CountMiceMice, Inbred C57BLMice, Inbred StrainsRecombinant ProteinsSpleenT-LymphocytesT-Lymphocytes, CytotoxicTransplantation, HomologousTumor Necrosis Factor-alphaConceptsBone marrow transplantationAllogeneic bone marrow transplantationAllogeneic BMT recipientsSystemic GVHDGVL effectHost diseaseBMT recipientsTumor necrosis factor alphaBeneficial GVL effectInduction of GVHDSeverity of graftToxicity of GVHDMurine BMT modelBone marrow inoculumNecrosis factor alphaT cell proliferationRecombinant human keratinocyte growth factorHuman keratinocyte growth factorKeratinocyte growth factorLeukemia effectLeukemia responseSerum levelsMarrow transplantationControl miceOrgan histopathology
2002
Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects
Reddy P, Teshima T, Hildebrandt G, Williams D, Liu C, Cooke K, Ferrara J. Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 2002, 101: 2877-2885. PMID: 12433681, DOI: 10.1182/blood-2002-08-2566.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsBone Marrow TransplantationFemaleGraft vs Host DiseaseGraft vs Leukemia EffectHumansInterferon-gammaInterleukin-18Leukemia, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLSTAT6 Transcription FactorSurvival RateT-LymphocytesTissue DonorsTrans-ActivatorsTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationPretreatment of donorsIL-18Acute GVHDAcute graftHost diseaseLeukemia effectTransplant donorsCytotoxic T lymphocyte activityAcute GVHD mortalityIL-18 pretreatmentDonor T cellsT lymphocyte activityBM transplant recipientsIL-4 secretionSTAT6-dependent mechanismIL-18 treatmentGVHD mortalityGVL effectPreserves graftTransplant recipientsInterleukin-18Marrow transplantationBM donors