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 cellsPhase 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