2014
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Shono Y, Tuckett A, Ouk S, Liou H, Altan-Bonnet G, Tsai J, Oyler J, Smith O, West M, Singer N, Doubrovina E, Pankov D, Undhad C, Murphy G, Lezcano C, Liu C, O'Reilly R, van den Brink M, Zakrzewski J. A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity. Cancer Discovery 2014, 4: 578-591. PMID: 24550032, PMCID: PMC4011979, DOI: 10.1158/2159-8290.cd-13-0585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression RegulationGraft vs Host DiseaseGraft vs Tumor EffectHematopoietic Stem Cell TransplantationHumansLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLProto-Oncogene Proteins c-relReceptors, Antigen, T-CellSmall Molecule LibrariesT-LymphocytesTransplantation, HomologousConceptsT cellsC-Rel activityAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEffector T cellsRegulatory T cellsIL-2 levelsStem cell transplantationAntigen-specific cytotoxicityC-Rel-deficient T cellsC-RelHuman T cellsT cell receptor activationGut homingGVT activityImmunomodulatory therapyInhibitor administrationCell transplantationTumor activityImmune systemReceptor activationPharmaceutical inhibitionSmall molecule-based inhibitionAlloactivationBroad suppression
2013
PLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD
Ghosh A, Holland A, Dogan Y, Yim N, Rao U, Young L, West M, Singer N, Lee H, Na I, Tsai J, Jenq R, Penack O, Hanash A, Lezcano C, Murphy G, Liu C, Sadelain M, Sauer M, Sant'Angelo D, van den Brink M. PLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD. Cancer Research 2013, 73: 4687-4696. PMID: 23733752, PMCID: PMC3732814, DOI: 10.1158/0008-5472.can-12-4699.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsBone Marrow TransplantationFlow CytometryGraft vs Host DiseaseGraft vs Tumor EffectKruppel-Like Transcription FactorsLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalPromyelocytic Leukemia Zinc Finger ProteinT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsPromyelocytic leukemia zinc fingerGVT effectInvariant natural killer T (iNKT) cellsAlloreactive donor T cellsAllogeneic bone marrow transplantationNatural killer T cellsTranscription factor promyelocytic leukemia zinc fingerKiller T cellsAlloreactive T cellsBone marrow transplantationConventional T cellsOverall improved outcomesLess GVHDLower GVHDPreserves graftTumor effectImproved survivalMarrow transplantationCytokine responsesImproved outcomesTumor relapseEffector functionsGVHDHost-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation
Toubai T, Sun Y, Luker G, Liu J, Luker K, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy K, Reddy P. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood 2013, 121: 4231-4241. PMID: 23520337, PMCID: PMC3656455, DOI: 10.1182/blood-2012-05-432872.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsTumor-specific antigensGVT responseAllo-HCTAPC subsetsDendritic cellsExperimental allogeneic bone marrow transplantationHost-derived antigen-presenting cellsAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationAlloantigen-specific responsesHost-derived CD8Donor T cellsHematopoietic cell transplantationBone marrow transplantationRelevant murine modelStimulation of TLR3Host diseaseTumor effectMarrow transplantationCell transplantationTumor responseSerious toxicityT cellsOptimal graft
2011
Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation
Lu S, Kappel L, Charbonneau-Allard A, Atallah R, Holland A, Turbide C, Hubbard V, Rotolo J, Smith M, Suh D, King C, Rao U, Yim N, Bautista J, Jenq R, Penack O, Na I, Liu C, Murphy G, Alpdogan O, Blumberg R, Macian F, Holmes K, Beauchemin N, van den Brink M. Ceacam1 Separates Graft-versus-Host-Disease from Graft-versus-Tumor Activity after Experimental Allogeneic Bone Marrow Transplantation. PLOS ONE 2011, 6: e21611. PMID: 21760897, PMCID: PMC3130781, DOI: 10.1371/journal.pone.0021611.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCarcinoembryonic AntigenCD8-Positive T-LymphocytesCell PolarityCell ProliferationCytotoxicity, ImmunologicDendritic CellsGraft vs Host DiseaseGraft vs Tumor EffectHumansIntegrinsIntestine, SmallLymphocyte ActivationLymphocyte CountLymphoid TissueMiceOrgan SpecificityRadiation Injuries, ExperimentalRadiation, IonizingTransplantation, HomologousConceptsAllogeneic bone marrow transplantationBone marrow transplantationDonor T cellsCD8 T cellsT cellsMarrow transplantationGVHD mortalityTumor activityExperimental allogeneic bone marrow transplantationInflammatory bowel disease modelCell adhesion molecule-1GVHD target tissuesRegulation of GVHDTarget tissuesT cell numbersAlloreactive T cellsAdhesion molecule-1T cell activationVariety of physiologicAllo-BMTSystemic GVHDHost diseaseSmall intestinal cryptsDonor graftsAllogeneic transplantation
2007
IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease
Ramirez-Montagut T, Chow A, Kochman A, Smith O, Suh D, Sindhi H, Lu S, Borsotti C, Grubin J, Patel N, Terwey T, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease. The Journal Of Immunology 2007, 179: 1669-1680. PMID: 17641033, DOI: 10.4049/jimmunol.179.3.1669.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMurine renal cell carcinomaT cellsCell carcinomaGVT activityHost diseaseRenca cellsIFN-gammaTumor activityAllogeneic bone marrow transplantation modelFas ligandAbsence of graftRecipients of IFNBone marrow transplantation modelMechanism of graftMembrane-bound TNF-alphaTumor-bearing miceLethal graftLethal GVHDSevere GVHDTNF-alphaTransplantation modelTransplanted miceLytic capacitySolid tumors