2024
The FLRT3-UNC5B checkpoint pathway inhibits T cell–based cancer immunotherapies
Prajapati K, Yan C, Yang Q, Arbitman S, Fitzgerald D, Sharee S, Shaik J, Bosiacki J, Myers K, Paucarmayta A, Johnson D, O’Neill T, Kundu S, Cusumano Z, Langermann S, Langenau D, Patel S, Flies D. The FLRT3-UNC5B checkpoint pathway inhibits T cell–based cancer immunotherapies. Science Advances 2024, 10: eadj4698. PMID: 38427724, PMCID: PMC10906930, DOI: 10.1126/sciadv.adj4698.Peer-Reviewed Original ResearchConceptsFibronectin leucine-rich transmembrane protein 3T cellsHuman T cellsCancer immunotherapyT cell-based cancer immunotherapyInhibit T cell activationT cell checkpointsActivated human T cellsT cell immunityT cell killingT cell activationHuman cancer modelsImmune-dependent mannerAxon guidance proteinsTarget such mechanismsCAR-TCoinhibitory receptorsGuidance proteinsTumor immunityClinical benefitCancer modelsTumor growthCancer cellsHuman cancersMonoclonal antibodiesLeukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice
Singh A, Mommers-Elshof E, Vijver S, Jansen J, Gonder S, Lebbink R, Bihan D, Farndale R, Boon L, Langermann S, Leusen J, Flies D, Meyaard L, Pascoal Ramos M. Leukocyte-associated immunoglobulin-like receptor-1 blockade in combination with programmed death-ligand 1 targeting therapy mediates increased tumour control in mice. Cancer Immunology, Immunotherapy 2024, 73: 16. PMID: 38236251, PMCID: PMC10796629, DOI: 10.1007/s00262-023-03600-6.Peer-Reviewed Original ResearchConceptsLeukocyte-associated immunoglobulin-like receptor-1Increase tumor controlTumor controlAnti-programmed death-ligand 1Mouse modelT cells in vitroMouse T cells in vitroIncreased tumor clearanceAnti-tumor responsesDeath-ligand 1Immunocompetent mouse modelReduced tumor burdenControl tumor growthHumanized mouse modelIn vivo tumor modelsWild type miceAssociated with tumor developmentPD-L1Tumor burdenTumor clearanceConventional immunotherapyImmunocompetent miceTumor outgrowthTherapy responseTumor microenvironment
2023
LAIR-1 agonism as a therapy for acute myeloid leukemia
Lovewell R, Hong J, Kundu S, Fielder C, Hu Q, Kim K, Ramsey H, Gorska A, Fuller L, Tian L, Kothari P, Paucarmayta A, Mason E, Meza I, Manzanarez Y, Bosiacki J, Maloveste K, Mitchell N, Barbu E, Morawski A, Maloveste S, Cusumano Z, Patel S, Savona M, Langermann S, Myint H, Flies D, Kim T. LAIR-1 agonism as a therapy for acute myeloid leukemia. Journal Of Clinical Investigation 2023, 133: e169519. PMID: 37966113, PMCID: PMC10650974, DOI: 10.1172/jci169519.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaLeukemic stem cellsMyeloid leukemiaPatient-derived xenograft modelsHealthy hematopoietic stem cellsStem cellsCare therapyLAIR-1LSC survivalAML blastsAgonist antibodyTherapeutic strategiesXenograft modelLeukemic cellsTherapeutic potentialHematopoietic stem cellsEffective eradicationTherapyLeukemiaCell deathAgonismSignaling programsCellsPresence of collagenAntibodies