2025
Phase 2, multicenter study of frontline maintenance therapy with lifileucel plus pembrolizumab in advanced non-small cell lung cancer.
Creelan B, Gettinger S, Chesney J, Sukari A, He K, Lee S, Garon E, Nieva J, Martin-Liberal J, Rodriguez Moreno J, Zugazagoitia J, Doger de Spéville B, Josephs D, Gibney G, Thomas S, Samhouri Y, Samakoglu S, Feng M, Finckenstein F, Schoenfeld A. Phase 2, multicenter study of frontline maintenance therapy with lifileucel plus pembrolizumab in advanced non-small cell lung cancer. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps8659.Peer-Reviewed Original ResearchMetastatic non-small cell lung cancerNon-small cell lung cancerTumor-infiltrating lymphocytesCell lung cancerStandard-of-careIL-2Advanced non-small cell lung cancerLung cancerIn vivo T-cell persistencePhase 2 open-label studyECOG performance status 0Treatment-emergent adverse eventsResponse rateFrontline maintenance therapySymptomatic brain metastasesComplete response rateDisease control rateDose of pembrolizumabPerformance status 0Platinum-doublet chemotherapyT cell persistenceCell transfer therapyCirculating tumor DNAEGFR wild-typeEffective targeted therapiesDissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing
Castellanos-Rueda R, Wang K, Forster J, Driessen A, Frank J, Martínez M, Reddy S. Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing. Science Advances 2025, 11: eadp4008. PMID: 39951542, PMCID: PMC11827634, DOI: 10.1126/sciadv.adp4008.Peer-Reviewed Original ResearchConceptsChimeric antigen receptorT-cell phenotypeT cell responsesT cell activationCAR T cell phenotypesCAR T-cell biologyModulate T cell responsesT cell persistenceCAR-T therapySingle-cell sequencingT cell functionT cell biologyCorrelated in vitroT therapyT cellsAntigen receptorClinical outcomesCD40 costimulationCancer treatmentPhenotypeSignaling domainMembrane-proximal domainCostimulationCD40Screening approach
2024
Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission
Bai Z, Feng B, McClory S, de Oliveira B, Diorio C, Gregoire C, Tao B, Yang L, Zhao Z, Peng L, Sferruzza G, Zhou L, Zhou X, Kerr J, Baysoy A, Su G, Yang M, Camara P, Chen S, Tang L, June C, Melenhorst J, Grupp S, Fan R. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature 2024, 634: 702-711. PMID: 39322664, PMCID: PMC11485231, DOI: 10.1038/s41586-024-07762-w.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric antigen receptor T cellsT cellsIL-4CAR T-cell dysfunctionChimeric antigen receptor T-cell productsCAR-T cell persistenceProteomic profiling of seraCAR-T cellsT cell persistenceT-cell therapyLong-term remissionT cell dysfunctionCAR-T productsType 2 cytokinesAntigen-specific activationT cell productionAssociated with patientsType 2 cellsDysfunctional subsetPotential therapeutic strategyCellular immunotherapyLeukemia remissionPatients relapseType 2 functionsFinding Your CAR The Road Ahead for Engineered T Cells
Chen P, Raghunandan R, Morrow J, Katz S. Finding Your CAR The Road Ahead for Engineered T Cells. American Journal Of Pathology 2024, 194: 1409-1423. PMID: 38697513, PMCID: PMC11284763, DOI: 10.1016/j.ajpath.2024.04.002.Peer-Reviewed Original ResearchConceptsChimeric antigen receptorCAR-T cellsAdoptive cellular therapyEngineered T cellsT cellsCellular therapyTumor cellsInfusion of CAR T cellsChimeric antigen receptor T cellsCAR-T cell cytotoxicityCAR-T cell persistenceCAR-T cell therapyT cell persistenceT-cell therapyT cell cytotoxicityTarget tumor antigensCytokine release syndromePathology laboratoryEvaluate side effectsTarget specific antigensTarget antigen identificationTransformative immunotherapyTumor antigensAntigen lossTumor microenvironment
2018
Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
Leone R, Sun I, Oh M, Sun I, Wen J, Englert J, Powell J. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunology, Immunotherapy 2018, 67: 1271-1284. PMID: 29923026, PMCID: PMC11028354, DOI: 10.1007/s00262-018-2186-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine A2 Receptor AntagonistsAnimalsAntigens, CDCD8-Positive T-LymphocytesColonic NeoplasmsFemaleGene Expression Regulation, NeoplasticImmunotherapyLymphocyte Activation Gene 3 ProteinLymphocytes, Tumor-InfiltratingMaleMelanoma, ExperimentalMiceMice, Inbred BALB CMice, Inbred C57BLProgrammed Cell Death 1 ReceptorReceptor, Adenosine A2AReceptors, Antigen, T-CellT-Lymphocytes, RegulatoryTumor Cells, CulturedTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsA2AR blockadePD-1T cellsImmune responseA2A receptorsCD39/CD73 axisTumor immune evasionEffector T cellsLAG-3 expressionRegulatory T cellsT cell persistenceTumor bearing miceAdenosine A2A receptorsMurine cancer modelsCoinhibitory receptorsCheckpoint blockadeCheckpoint therapyRegulatory cellsLymph nodesImmunologic responseImmunotherapy regimensInflammatory milieuPharmacologic blockadeA2AR antagonistAdenosine levels
2015
A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control
Xin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control. Cell Reports 2015, 13: 1118-1124. PMID: 26527008, PMCID: PMC4859432, DOI: 10.1016/j.celrep.2015.09.069.Peer-Reviewed Original ResearchConceptsCD8 T cellsChronic viral infectionsBATF expressionT cellsIL-21Chronic infectionEffector functionsViral infectionCD8 T cell effector functionsAnti-viral effector functionsCD8 T cell responsesCD8 T cell immunityT cell effector functionT cell immunityCD4 T cellsT cell responsesCell effector functionsT cell persistenceT cell maintenanceBlimp-1 expressionCD8 responsesCD4 helpCell immunityViral controlTranscription factor expression
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