2025
The efficacy of METTL3 inhibition in pre-clinical models of MDS and AML.
Kenworthy C, Wei M, VanOudenhove J, Busarello E, Ramirez Amarilla C, Paul S, Cruz J, Baassiri A, Maul-Newby H, Biancon G, Tebaldi T, Halene S. The efficacy of METTL3 inhibition in pre-clinical models of MDS and AML. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.e18584.Peer-Reviewed Original ResearchAcute myeloid leukemiaMyelodysplastic syndromeInnate immune responseImmune signaturesTransplantation modelModel of myelodysplastic syndromeMurine models of leukemiaPreclinical anti-tumour efficacyImmune responseInnate immune cell subsetsSolid tumor clinical trialsSplicing factorsCompetitive transplant modelImmune checkpoint inhibitionMouse solid tumor modelsDouble-stranded RNAMyelodysplastic syndrome patientsInnate immune signaturesAnti-tumor efficacyImmune cell subsetsMyelodysplastic syndromes pathogenesisDriver genesSolid tumor modelsPre-clinical modelsModels of leukemia
2024
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Leighl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockadeSuccessful management of pre-existing psoriatic arthritis through targeting the IL-23/IL-17 axis in cancer patients receiving immune checkpoint inhibitor therapy: a case series
Li Y, Msaouel P, Campbell M, Hwu P, Diab A, Kim S. Successful management of pre-existing psoriatic arthritis through targeting the IL-23/IL-17 axis in cancer patients receiving immune checkpoint inhibitor therapy: a case series. RMD Open 2024, 10: e004308. PMID: 39214611, PMCID: PMC11367333, DOI: 10.1136/rmdopen-2024-004308.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune checkpoint inhibitor therapyAnti-IL-17A antibodyAdverse eventsAnti-PD-1 antibody monotherapyInterleukin (IL)-17/IL-23 axisPsoriatic arthritisImmune checkpoint inhibitor treatmentPD-1 antibody therapyResponse to ICI therapyImmune-related adverse eventsIL-23/IL-17 axisImmune checkpoint inhibitor exposureIL-17/23 axisAnti-CTLA-4Checkpoint inhibitor therapyCell renal cell carcinomaAnti-IL-17AAnti-IL-23 antibodyAssociated with adverse eventsPre-existing psoriasisAnti-tumor efficacyIL-23/IL-17Renal cell carcinomaICI therapyNovel immunotherapeutics against LGR5 to target multiple cancer types
Chen H, Mueller N, Stott K, Kapeni C, Rivers E, Sauer C, Beke F, Walsh S, Ashman N, O’Brien L, Rafati Fard A, Ghodsinia A, Li C, Joud F, Giger O, Zlobec I, Olan I, Aitken S, Hoare M, Mair R, Serrao E, Brenton J, Garcia-Gimenez A, Richardson S, Huntly B, Spring D, Skjoedt M, Skjødt K, de la Roche M, de la Roche M. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine 2024, 16: 2233-2261. PMID: 39169164, PMCID: PMC11393416, DOI: 10.1038/s44321-024-00121-2.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaColorectal cancerTarget multiple cancer typesBispecific T-cell engagerCell killing in vitroChimeric antigen receptorT-cell engagersCancer cells in vitroPre-B-ALLAnti-tumor efficacyCancer cell killing in vitroKilling in vitroCells in vitroAntibody-drug conjugatesMultiple cancer typesLGR5 overexpressionTumor burdenAntigen receptorMurine modelNovel immunotherapeuticsCancer modelsTumor cellsEffective modalityEffective tumorLgr5
2023
1070 ‘Decoy-resistant’ IL-18 in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma
Schoenfeld D, Djureinovic D, Zhang L, Mann J, Huck J, Jilaveanu L, Ring A, Kluger H. 1070 ‘Decoy-resistant’ IL-18 in combination with CTLA-4 blockade enhances anti-tumor efficacy in preclinical models of renal cell carcinoma. 2023, a1177-a1179. DOI: 10.1136/jitc-2023-sitc2023.1070.Peer-Reviewed Original ResearchEnhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition
Han R, Ling C, Wang Y, Lu L. Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition. Cancer Cell International 2023, 23: 203. PMID: 37716965, PMCID: PMC10504701, DOI: 10.1186/s12935-023-03051-0.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsHepatocellular carcinomaCheckpoint inhibitorsHCC treatmentPD-1/PD-L1 inhibitionPD-1/PD-L1 inhibitorsHDAC2 inhibitorsTreatment of HCCPD-L1 inhibitionAnti-cancer immunityPD-L1 inhibitorsAnti-tumor efficacyNew combination strategiesPD-L1Clinical benefitHigh morbidityTherapeutic effectSolid cancersEffective treatmentLatest evidenceNuclear translocationTreatmentInhibitorsCombination strategiesEfficacy1091 Improving the anti-tumor efficacy of immunomodulator MPLA via biodegradable nanoparticle delivery
Chang J, Shin K, Lewis J, Suh H, Bosenberg M, Saltzman W, Girardi M. 1091 Improving the anti-tumor efficacy of immunomodulator MPLA via biodegradable nanoparticle delivery. Journal Of Investigative Dermatology 2023, 143: s187. DOI: 10.1016/j.jid.2023.03.1103.Peer-Reviewed Original ResearchNanoparticle deliveryAnti-tumor efficacyAnti-tumor Efficacy of CD19 CAR-T in a Raji B Cell Xenografted Mouse Model
Xiao Q, Su X. Anti-tumor Efficacy of CD19 CAR-T in a Raji B Cell Xenografted Mouse Model. Bio-protocol 2023, 13: e4655. PMID: 37113332, PMCID: PMC10127058, DOI: 10.21769/bioprotoc.4655.Peer-Reviewed Original ResearchCAR T cellsCD19 CAR T cellsRefractory B-cell malignanciesCell-induced tumorsChimeric antigen receptorImmune-deficient miceAnti-tumor efficacyB-cell malignanciesMouse xenograft modelTumor-killing abilityXenografted mouse modelCAR-TsT therapyHealthy donorsCD19-CARMouse modelXenograft modelTumor growthPreclinical researchTumor cellsCancer treatmentAntigen receptorMiceCellsMalignancyDeletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy
Trefny M, Kirchhammer N, Auf der Maur P, Natoli M, Schmid D, Germann M, Fernandez Rodriguez L, Herzig P, Lötscher J, Akrami M, Stinchcombe J, Stanczak M, Zingg A, Buchi M, Roux J, Marone R, Don L, Lardinois D, Wiese M, Jeker L, Bentires-Alj M, Rossy J, Thommen D, Griffiths G, Läubli H, Hess C, Zippelius A. Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. Nature Communications 2023, 14: 86. PMID: 36732507, PMCID: PMC9895440, DOI: 10.1038/s41467-022-35583-w.Peer-Reviewed Original ResearchConceptsT cell exhaustionT cellsTumor-specific T cellsCD8 T cell exhaustionT cells in vivoPreventing T cell exhaustionCellular cancer immunotherapyExhausted T cellsT-cell immunotherapyAnti-tumor immunityChronic antigenic stimulationAnti-tumor efficacyT cell signalingIFNg secretionCancer immunotherapyMemory differentiationTCR/CD28 stimulationTherapeutic optionsAntigenic stimulationReduced expressionCRISPR-Cas9 screensCD8ImmunotherapySorting nexin 9Stimulation
2021
766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs)
Bhagchandani S, Milling L, Liu B, Fessenden T, Spranger S, Johnson J, Irvine D. 766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs). Journal For ImmunoTherapy Of Cancer 2021, 9: a801-a801. DOI: 10.1136/jitc-2021-sitc2021.766.Peer-Reviewed Original ResearchTLR reporter cellsSystemic deliveryAnti-PD-1 antibody treatmentMC38 colon cancer modelImidazoquinoline derivativesToll-like receptor agonistsSerum cytokine levelsMaximum tolerable doseSystemic side effectsImproved survival ratesReporter cellsAnti-tumor efficacyColon cancer modelCytokine levelsMetastatic diseaseTLR agonistsTLR7/8 agonistAntibody treatmentTLR activationTreatment of cancerTolerable doseReceptor agonistIntravenous administrationTopical solutionSide effects
2020
Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer.
Powderly J, Chmielowski B, Brahmer J, Piha-Paul S, Bowyer S, LoRusso P, Catenacci D, Wu C, Barve M, Chisamore M, Nasrah N, Johnson D, Ho W. Phase I/II dose-escalation and expansion study of FLX475 alone and in combination with pembrolizumab in advanced cancer. Journal Of Clinical Oncology 2020, 38: tps3163-tps3163. DOI: 10.1200/jco.2020.38.15_suppl.tps3163.Peer-Reviewed Original ResearchCheckpoint inhibitorsExpansion cohortT cellsPhase 1 dose escalationAnti-tumor immune responseTumor microenvironmentPhase I/IIPreliminary anti-tumor activityCohort expansion phaseCohort expansion studyPhase 2 dosePredominant chemokine receptorPhase 1/2 studyDose-escalation phaseEffector T cellsRegulatory T cellsAnti-tumor responseTumor-associated macrophagesAnti-tumor efficacyAnti-tumor activityEligible subjectsDendritic cellsDose escalationPhase 1/2Advanced cancer
2019
Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responses
Jiang X, Fedorova O, Linehan M, Dong H, Pyle A, Iwasaki A. Intratumoral delivery of RIG-I agonist induces robust anti-tumor immune responses. The Journal Of Immunology 2019, 202: 194.28-194.28. DOI: 10.4049/jimmunol.202.supp.194.28.Peer-Reviewed Original ResearchAnti-tumor efficacyRobust anti-tumor immune responseAnti-tumor immune responseTumor microenvironmentNucleic acid-sensing pathwaysT-cell depletionTumor-infiltrating lymphocytesCytosolic nucleic acid-sensing pathwaysB16 melanoma growthVivo anti-tumor efficacyPromising therapeutic agentLong-term survivalRemarkable antitumor effectImmunogenic tumorsInnate cellsCell depletionCancer immunotherapyMouse survivalImmune responseTumor volumeCombination treatmentIntratumoral deliveryAntitumor effectsMelanoma growthTumor subtypes
2006
2659 Inhibition of VEGFR-1, -2, and -3 Signaling by AZD2171 Enhances the Anti-Tumor Efficacy of Radiation Therapy in a Mouse Xenograft Model
Imagumbai T, Komaki R, Milas L, Valdecanas D, Furutani K, Ryan A, Jürgensmeier J, Ang K, Herbst R, O’Reilly M. 2659 Inhibition of VEGFR-1, -2, and -3 Signaling by AZD2171 Enhances the Anti-Tumor Efficacy of Radiation Therapy in a Mouse Xenograft Model. International Journal Of Radiation Oncology • Biology • Physics 2006, 66: s576. DOI: 10.1016/j.ijrobp.2006.07.1074.Peer-Reviewed Original Research
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