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
Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity
Ghosh A, Dogan Y, Moroz M, Holland A, Yim N, Rao U, Young L, Tannenbaum D, Masih D, Velardi E, Tsai J, Jenq R, Penack O, Hanash A, Smith O, Piersanti K, Lezcano C, Murphy G, Liu C, Palomba M, Sauer M, Sadelain M, Ponomarev V, van den Brink M. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal Of Clinical Investigation 2013, 123: 2654-2662. PMID: 23676461, PMCID: PMC3668849, DOI: 10.1172/jci66301.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell Line, TumorCytotoxicity, ImmunologicGraft RejectionGraft vs Host DiseaseHEK293 CellsHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasm TransplantationT-LymphocytesTNF-Related Apoptosis-Inducing LigandConceptsGVT responseT cellsAllo-HSCTAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCellular therapyAbsence of GVHDDR5-dependent mannerDonor T cellsAlloreactive T cellsStem cell transplantationChronic lymphocytic leukemia cellsPrecursor T cellsThird-party donorsLymphocytic leukemia cellsApoptosis-inducing ligandGVT activityHost diseaseCell transplantationCurative potentialTumor responseGVHDCertain malignanciesMouse modelHuman leukemia cell lines
2008
IL-17 contributes to CD4-mediated graft-versus-host disease
Kappel L, Goldberg G, King C, Suh D, Smith O, Ligh C, Holland A, Grubin J, Mark N, Liu C, Iwakura Y, Heller G, van den Brink M. IL-17 contributes to CD4-mediated graft-versus-host disease. Blood 2008, 113: 945-952. PMID: 18931341, PMCID: PMC2630280, DOI: 10.1182/blood-2008-08-172155.Peer-Reviewed Original ResearchConceptsRecipients of ILT cellsGVHD mortalityHost diseaseIL-17Proinflammatory cytokinesAllogeneic bone marrow transplantAllogeneic BMT modelIL-17 contributesDonor T cellsBone marrow transplantWhole T cellsT-cell recipientsAcute graftGVHD developmentGVT activityAllograft rejectionTh17 cellsIL-17FIL-22Interleukin-17Marrow transplantAutoimmune diseasesTh1 cellsLymphoid organs
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 tumorsAbsence of donor T-cell–derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity
Borsotti C, Franklin A, Lu S, Kim T, Smith O, Suh D, King C, Chow A, Liu C, Alpdogan O, van den Brink M. Absence of donor T-cell–derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity. Blood 2007, 110: 783-786. PMID: 17395784, PMCID: PMC1924485, DOI: 10.1182/blood-2006-10-054510.Peer-Reviewed Original ResearchConceptsT cellsTNF-alpha converting enzymeGVT activityHost diseaseTumor activityAllogeneic bone marrow transplantationDonor T cellsBone marrow transplantationMurine BMT modelWild-type T cellsLess GVHDMarrow transplantationBMT modelNecrosis factorEndogenous TNFSoluble TNFGVHDConverting enzymeGraftTNFDiseaseRecipientsSoluble moleculesCellsMemTNF
2005
Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine
Waldman E, Lu S, Hubbard V, Kochman A, Eng J, Terwey T, Muriglan S, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. Absence of β7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood 2005, 107: 1703-1711. PMID: 16291587, PMCID: PMC1895413, DOI: 10.1182/blood-2005-08-3445.Peer-Reviewed Original ResearchConceptsHematopoietic stem cell transplantationLess GVHD morbidityT cell infiltrationT cellsGVHD morbidityGVT activityHost diseaseDonor T-cell infiltrationDonor T cellsAlloreactive T cellsStem cell transplantationWild-type T cellsOverall significant decreaseIntestinal graftIntestinal GVHDLess graftBeta7 integrinCell transplantationCytokine productionAlpha4beta7 integrinIntact activationTumor experimentsMorbidityClinical potentialGraftCCR2 is required for CD8-induced graft-versus-host disease
Terwey T, Kim T, Kochman A, Hubbard V, Lu S, Zakrzewski J, Ramirez-Montagut T, Eng J, Muriglan S, Heller G, Murphy G, Liu C, Budak-Alpdogan T, Alpdogan O, van den Brink M. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005, 106: 3322-3330. PMID: 16037386, PMCID: PMC1895329, DOI: 10.1182/blood-2005-05-1860.Peer-Reviewed Original ResearchConceptsCC chemokine receptor 2Hematopoietic stem cell transplantationDevelopment of GVHDT cellsT cell migrationHost diseaseAllogeneic hematopoietic stem cell transplantationDonor-derived T cellsControl of CD8Donor-derived CD8GVHD target organsMurine bone marrow transplantation modelBone marrow transplantation modelStem cell transplantationChemokine receptor 2IFN-gamma productionWild-type CD8Alloreactive proliferationDonor CD8GVHD morbidityGVT activityTumor effectMajor complicationsCCR2 signalingCell transplantation
2003
LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease
Petrovic A, Alpdogan O, Willis L, Eng J, Greenberg A, Kappel B, Liu C, Murphy G, Heller G, van den Brink M. LPAM (α4β7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood 2003, 103: 1542-1547. PMID: 14563643, DOI: 10.1182/blood-2003-03-0957.Peer-Reviewed Original ResearchConceptsDonor T cellsT cellsMurine allogeneic bone marrow transplantation modelAllogeneic bone marrow transplantation modelAlloreactive donor T cellsGut-associated lymphoid tissueAdhesion moleculesMucosal addressin cell adhesion moleculeGVHD target organsMesenteric lymph nodesAlloreactive T cellsBone marrow transplantation modelMucosal lymphoid organsHigh endothelial venulesGVHD morbidityGVT activityIntestinal graftIntestinal GVHDLess graftLess GVHDHost diseaseLymph nodesDisease morbidityLymphoid organsLymphoid tissue