MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers
Eguren-Santamaria I, de Piérola E, Camps G, Martín-Muñoz P, Campos M, Cuculescu D, Aguilera-Buenosvinos I, López I, Salido-Vallejo R, Alexandru R, De Andrea C, Álvarez-Gigli L, Berraondo P, Melero I, Sanmamed M. MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers. Journal For ImmunoTherapy Of Cancer 2024, 12: e008516. PMID: 39244214, PMCID: PMC11381650, DOI: 10.1136/jitc-2023-008516.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHuman peripheral blood mononuclear cellsT-cell engagersNSG miceMajor histocompatibility complexSevere XGVHDImmunodeficient miceAntitumor effectTumor rejectionImmunotherapy agentsAntitumor activityAntitumor efficacy of immune checkpoint inhibitorsEfficacy of immune checkpoint inhibitorsHT29 human colon carcinoma cellsLong-term antitumor efficacyDevelopment of cancer immunotherapyAdministration of nivolumabImmune checkpoint inhibitorsCancer immunotherapy agentsT cell clonesHuman colon carcinoma cellsAlanine aminotransferase levelsMajor histocompatibility complex class IBlood mononuclear cellsHuman immune cellsShort-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-regulated