2021
493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors
Johnson M, Lopez J, LoRusso P, Bauman J, Haggstrom D, Lagkadinou E, Bajaj G, Türeci Ö, Adams H, Şahin U, Fu Y, Ahmadi T, Rohrberg K. 493 First-in-human phase 1/2 trial to evaluate the safety and initial clinical activity of DuoBody®-CD40×4–1BB (GEN1042) in patients with advanced solid tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a525-a525. DOI: 10.1136/jitc-2021-sitc2021.493.Peer-Reviewed Original ResearchAdvanced solid tumorsDose-limiting toxicityAdverse eventsSolid tumorsPartial responseLung cancerAntitumor activityNon-CNS solid tumorsTreatment-related adverse eventsEffector memory T cellsDrug-related gradeInitial clinical activityPD-1 inhibitorsPhase 1/2 trialTumor-specific immunityMemory T cellsCell lung cancerFavorable safety profilePreliminary antitumor activityNeuroendocrine lung cancerBest overall responseEnd of infusionCommon cancer typesEthics committees/institutional review boardsInstitutional review board
2020
Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells
Oh M, Sun I, Zhao L, Leone R, Sun I, Xu W, Collins S, Tam A, Blosser R, Patel C, Englert J, Arwood M, Wen J, Chan-Li Y, Tenora L, Majer P, Rais R, Slusher B, Horton M, Powell J. Targeting glutamine metabolism enhances tumor specific immunity by modulating suppressive myeloid cells. Journal Of Clinical Investigation 2020, 130: 3865-3884. PMID: 32324593, PMCID: PMC7324212, DOI: 10.1172/jci131859.Peer-Reviewed Original ResearchConceptsMyeloid-derived suppressor cellsTumor-associated macrophagesRecruitment of MDSCsGlutamine metabolismMyeloid cellsTumor growthTumor microenvironmentSuppressive myeloid cellsSuppressive immune cellsTumor-specific immunityMyeloid-derived cellsActivation-induced cell deathDevelopment of metastasesImmunogenic cell deathCell deathAntitumor immunityKynurenine levelsSuppressor cellsIDO expressionSpecific immunityImmune cellsTumor glutamine metabolismImmune evasionInflammatory macrophagesSmall molecule inhibitorsShort-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade
Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remírez A, Lecanda F, Alignani D, Lasarte J, Macaya I, Senent Y, Bértolo C, Sainz C, Gil-Bazo I, Eguren-Santamaría I, Lopez-Picazo J, Gonzalez A, Perez-Gracia J, de Andrea C, Vicent S, Sanmamed M, Montuenga L, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nature Cancer 2020, 1: 75-85. PMID: 35121837, DOI: 10.1038/s43018-019-0007-9.Peer-Reviewed Original ResearchConceptsPD-1 blockadeCell death protein 1 (PD-1) pathwayPD-1 immune checkpoint blockadeCD8/Treg ratioHigh IGF-1R expressionInsulin-like growth factor-1Cell lung cancer treatmentIGF-1 levelsPD-1 inhibitionImmune checkpoint blockadeTumor-specific immunityCell lung cancerIGF-1R expressionHigher plasma levelsLung cancer progressionLung cancer treatmentIGF-1 receptorGrowth factor-1Protein 1 pathwayTreg ratioCD8 cellsCheckpoint blockadePD-1Syngeneic modelLung cancer
2019
Administration of BPX-501 Cells Following Αβ T and B-Cell-Depleted HLA Haploidentical HSCT (haplo-HSCT) in Children with Acute Leukemias (AL)
Galaverna F, Ruggeri A, Merli P, Kapoor N, Agarwal-Hashmi R, Aquino V, Jacobsohn D, Qasim W, Nemecek E, Krishnamurti L, Manwani D, Kuhn M, Locatelli F, Naik S. Administration of BPX-501 Cells Following Αβ T and B-Cell-Depleted HLA Haploidentical HSCT (haplo-HSCT) in Children with Acute Leukemias (AL). Transplantation And Cellular Therapy 2019, 25: s15-s16. DOI: 10.1016/j.bbmt.2018.12.082.Peer-Reviewed Original ResearchSteroid-resistant GVHDAcute leukemiaEvaluable ptsEfficacy outcomesΑβ TT cellsB cellsPediatric ptsBetter overall clinical responsePost-transplant GvHD prophylaxisHigh-risk acute leukemiaHLA-haploidentical HSCTOverall clinical responseSubset of ptsPrimary graft failureTumor-specific immunityHost disease symptomsInducible caspase-9 safety switchAllogeneic HSCTEnhanced graftGVHD prophylaxisHaplo-HSCTHaploidentical HSCTLeukemic effectsPlatelet engraftment
2018
Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy
Miller NJ, Church CD, Fling SP, Kulikauskas R, Ramchurren N, Shinohara MM, Kluger HM, Bhatia S, Lundgren L, Cheever MA, Topalian SL, Nghiem P. Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy. Journal For ImmunoTherapy Of Cancer 2018, 6: 131. PMID: 30482247, PMCID: PMC6258401, DOI: 10.1186/s40425-018-0450-7.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalB-LymphocytesBiomarkers, TumorCarcinoma, Merkel CellHumansImmunomodulationLymphocyte ActivationMerkel cell polyomavirusMolecular Targeted TherapyPolyomavirus InfectionsProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellT-Cell Antigen Receptor SpecificityT-LymphocytesTreatment OutcomeTumor Virus InfectionsConceptsAnti-PD-1 therapyPeripheral blood mononuclear cellsB cell responsesCell responsesCell carcinomaT cellsDiverse T-cell responsePD-1 blockade therapyPre-treatment tumor biopsiesVirus-specific T cellsT-cell receptor clonalityVP-MCCCancer-specific immunityIntratumoral TCR repertoirePD-1 blockadeTumor-specific immunityT cell responsesBlood mononuclear cellsMerkel cell carcinomaAggressive skin cancerBackgroundMerkel cell carcinomaVirus-negative tumorsMerkel cell polyomavirusPresence of antigenMethodsImmune responses
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