2023
Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR/Cas9 Enhances Cytotoxicity and Cytokine Production.
Dahlvang J, Dick J, Sangala J, Kennedy P, Pomeroy E, Snyder K, Moushon J, Thefaine C, Wu J, Hamilton S, Felices M, Miller J, Walcheck B, Webber B, Moriarity B, Hart G. Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR/Cas9 Enhances Cytotoxicity and Cytokine Production. The Journal Of Immunology 2023, 210: 1108-1122. PMID: 36881874, PMCID: PMC10073313, DOI: 10.4049/jimmunol.2200488.Peer-Reviewed Original ResearchMeSH KeywordsAntibody-Dependent Cell CytotoxicityCRISPR-Cas SystemsCytokinesCytomegalovirusCytomegalovirus InfectionsHumansKiller Cells, NaturalSyk KinaseConceptsAb-dependent cellular cytotoxicityAdaptive NK cellsPrimary human NK cellsNK cellsHuman NK cellsCytokine productionFcRγ chainSHP-1Loss of sykTarget cell conjugationNK cell phenotypeReduced cytokine productionTNF-α productionCRISPR/Cas9 systemPhosphatase SHP-1Transcription factor PLZFCell conjugationCellular cytotoxicityImmune stateCD2 expressionSyk expressionLack expressionEnhances CytotoxicityCas9 systemEnhanced cytotoxicity
2021
Simultaneous Engagement of Tumor and Stroma Targeting Antibodies by Engineered NK-92 Cells Expressing CD64 Controls Prostate Cancer Growth
Hintz H, Snyder K, Wu J, Hullsiek R, Dahlvang J, Hart G, Walcheck B, LeBeau A. Simultaneous Engagement of Tumor and Stroma Targeting Antibodies by Engineered NK-92 Cells Expressing CD64 Controls Prostate Cancer Growth. Cancer Immunology Research 2021, 9: 1270-1282. PMID: 34452926, PMCID: PMC9119026, DOI: 10.1158/2326-6066.cir-21-0178.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerAntibody-dependent cell-mediated cytotoxicityCastration-resistant prostate cancerEffector-target cell ratioNatural killer cellsCell-mediated cytotoxicityIsotype control antibodyNK-92 cellsCombination of mAbsNK-92MI cellsProstate cancer growthCalcium signal transducer 2NK cell linesTumor-associated calcium signal transducer 2Fibroblast activation protein alphaOverall survivalNK cellsCell activation mechanismsImmunotherapy responseKiller cellsNK-92MICombination therapyPrior sensitizationControl antibodyProstate cancer