2024
The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
Feng B, Bai Z, Zhou X, Zhao Y, Xie Y, Huang X, Liu Y, Enbar T, Li R, Wang Y, Gao M, Bonati L, Peng M, Li W, Tao B, Charmoy M, Held W, Melenhorst J, Fan R, Guo Y, Tang L. The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer. Nature 2024, 634: 712-720. PMID: 39322665, PMCID: PMC11485240, DOI: 10.1038/s41586-024-07962-4.Peer-Reviewed Original ResearchCD8+ T cellsMammalian target of rapamycinCancer immunotherapyT cellsNext-generation cancer immunotherapyAdoptive T-cell transferImmune checkpoint blockade therapyLong-term complete remissionCurrent cancer immunotherapiesCheckpoint blockade therapyInduce durable remissionsT-cell transferCD8+ TCytokine-based immunotherapyType 2 cytokinesXenograft tumor modelBlockade therapyDurable remissionsComplete remissionAntitumour efficacyTumor modelTarget of rapamycinInterleukin-4Immune responseCD8Single-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 functions
2023
Single-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission
Bai Z, Feng B, Mcclory S, Diorio C, Zhao Z, Tang L, Melenhorst J, June C, Grupp S, Fan R. Single-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission. Blood 2023, 142: 352. DOI: 10.1182/blood-2023-179480.Peer-Reviewed Original ResearchChimeric antigen receptor T cellsCAR-T cellsChimeric antigen receptorType 2 cytokinesB-cell aplasiaT cellsAcute lymphocytic leukemiaCAR-T persistenceIL-4CAR-TType 1Validation cohortCAR T infusionSurvival of tumor-bearing miceDiscovery cohortPersistent CAR T cellsDose of tumor cellsLevels of type 2 cytokinesType 2 cytokine levelsNSG mouse modelPediatric ALL patientsLong-term remissionReduced tumor burdenT cell longevityType 1 cytokines