Targeting T-cell costimulation to the surface of tumor cells.
Eguren-Santamaría I, Sanmamed M, Molero-Glez P, Perez-Gracia J, Melero I. Targeting T-cell costimulation to the surface of tumor cells. Clinical Cancer Research 2024, of1-of3. PMID: 39531541, DOI: 10.1158/1078-0432.ccr-24-3003.Peer-Reviewed Original ResearchT lymphocytesTumor cellsTargeting T-cell costimulationSurface of tumor cellsT cell costimulationProportion of patientsT cell activationAntitumor responseT cellsSolid tumorsSurface antigensActivator receptorSignal 2CostimulationTumorTarget specificityCellsCD137HER2Novel evidencePatientsAntigenReceptorsShort-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism
Eguren-Santamaría I, Rodríguez I, Herrero-Martin C, de Piérola E, Azpilikueta A, Sánchez-Gregorio S, Bolaños E, Gomis G, Molero-Glez P, Chacón E, Mínguez J, Chiva S, Diez-Caballero F, de Andrea C, Teijeira Á, Sanmamed M, Melero I. Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism. OncoImmunology 2024, 13: 2373519. PMID: 38988823, PMCID: PMC11236292, DOI: 10.1080/2162402x.2024.2373519.Peer-Reviewed Original ResearchConceptsTumor fragmentsImmunotherapy combinationsIFNg productionActivation markersClinical response to PD-1 blockadeResponse to PD-1 blockadeAgonistic anti-CD137 mAbAnti-PD-1 treatmentAnti-CD137 mAbAnti-PD-1PD-1 blockadeSyngeneic immunocompetent miceInfiltrating T cellsShort-term cultureUnmet medical needAnti-CD137Contralateral tumorsBilateral tumorsCancer immunotherapyTissue culture supernatantsImmunocompetent miceSolid malignanciesT cellsMAb combinationsMouse tumorsUp-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulatedPhase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure
Spreafico A, Couselo E, Irmisch A, Bessa J, Au-Yeung G, Bechter O, Svane I, Sanmamed M, Gambardella V, McKean M, Callahan M, Dummer R, Klein C, Umaña P, Justies N, Heil F, Fahrni L, Opolka-Hoffmann E, Waldhauer I, Bleul C, Staack R, Karanikas V, Fowler S. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure. Frontiers In Oncology 2024, 14: 1346502. PMID: 38577337, PMCID: PMC10991832, DOI: 10.3389/fonc.2024.1346502.Peer-Reviewed Original ResearchTreatment-related adverse eventsAnti-drug antibodiesCytokine release syndromeFirst-in-humanT-cell engagersCheckpoint inhibitorsMetastatic melanomaT cellsDrug exposureDevelopment of anti-drug antibodiesActive drugImmune responseFirst-in-human studyDrug activity in vitroDose-escalation studyDose-escalation trialTumor necrosis factor-alphaB cell interactionsImpact of immune responsesActive drug exposureNecrosis factor-alphaAnti-tumor activityLoss of efficacyAssociated with developmentDose escalation