2025
Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma
Yang L, Pham K, Xi Y, Wu Q, Liu D, Robertson K, Liu C. Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma. PLOS ONE 2025, 20: e0317401. PMID: 39841705, PMCID: PMC11753693, DOI: 10.1371/journal.pone.0317401.Peer-Reviewed Original ResearchConceptsGlypican-3Hepatocellular carcinomaCAR-NKNatural killerCell linesCAR-NK therapyCAR-NK cellsTreatment of hepatocellular carcinomaNK cell lineAnti-tumor effectsCancer-related mortalitySuppressed tumor growthPrimary liver cancerInfluence therapeutic outcomesCells in vitroHepatocellular carcinoma treatmentHepG2 cells in vitroNK92MI cellsImmunotherapy strategiesNSG miceImmunotherapy targetOncofetal glycoproteinTherapy resistanceImprove patient outcomesPoor prognosis
2024
Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors.
Falchook G, LoRusso P, Goldman J, El-Khoueiry A, Tolcher A, Xing Y, Henry J, Keam B, Kim D, Kim T, Kim H, Hong M, Kim M, Lee D, Lee S, Jeon J, Hayslip J, Xu C, Garon E. Phase 1 trial safety and efficacy of ragistomig, a bispecific antibody targeting PD-L1 and 4-1BB, in advanced solid tumors. Journal Of Clinical Oncology 2024, 42: 2529-2529. DOI: 10.1200/jco.2024.42.16_suppl.2529.Peer-Reviewed Original ResearchTreatment related adverse eventsClinical benefit rateOverall response ratePD-L1Dose levelsPD-(L)1Complete responsePartial responseSolid tumorsHead and neck squamous cellAntibody targeting PD-L1Treated with checkpoint inhibitorsActivation of T cellsDose-limiting toxicityPre-treated patientsPD-(L)1 inhibitorsDose-expansion cohortRelapsed/refractory solid tumorsWeight-based dosingLines of treatmentPD-L1 antagonistsRelated adverse eventsAnti-tumor effectsDose-dependent increaseMultiple tumor typesThe CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells
Liao X, Li W, Zhou H, Rajendran B, Li A, Ren J, Luan Y, Calderwood D, Turk B, Tang W, Liu Y, Wu D. The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells. Nature Communications 2024, 15: 603. PMID: 38242867, PMCID: PMC10798966, DOI: 10.1038/s41467-024-44885-0.Peer-Reviewed Original ResearchConceptsCD8+ T cellsT cellsCancer immunotherapyMouse CD8+ T cellsAnti-tumor immunityTumor growth inhibition abilityAnti-tumor effectsInhibition of neddylationCD8Effector functionsTCR stimulationIL2 signalingCentral signaling pathwaysCore signaling pathwaysEffector activityNegative regulatory mechanismsTranslational implicationsImmunotherapyGrowth inhibition abilityCytokine signalingTCRProteomic alterationsSignaling pathwayCancerCRISPR-based screens
2023
Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory.
Alvero A, Fox A, Madina B, Krady M, Gogoi R, Chehade H, Nakaar V, Almassian B, Yarovinsky T, Rutherford T, Mor G. Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory. Cancer Immunology Research 2023, 12: 261-274. PMID: 38078853, PMCID: PMC11027955, DOI: 10.1158/2326-6066.cir-23-0127.Peer-Reviewed Original ResearchPD-L1Immunological memoryImmune surveillanceLong-term anti-tumor effectsAnti-tumor immunological memoryAnti-tumor immune responseImmune modulatory capacityAnti-tumor responseOvarian cancer patientsAnti-tumoral responseAnti-tumor effectsImmune regulatory genesSelf-amplifying RNAVirus-like vesiclesPotent CD8MDSC expansionAdaptive armsCurrent immunotherapiesOncolytic capacityPrevent recurrenceAntitumor cytokinesCancer patientsImmune modulationImmune modulatorsOncolytic effectSelf‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma
Li Y, Zhao Q, Zhu X, Zhou L, Song P, Liu B, Tian D, Chen Q, Zhou J, Deng G. Self‐Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma. CNS Neuroscience & Therapeutics 2023, 30: e14528. PMID: 38044793, PMCID: PMC11017454, DOI: 10.1111/cns.14528.Peer-Reviewed Original ResearchBlood-brain barrierP-gp inhibitorsCerebral vascular endothelial cellsStrong anti-tumor effectsCommon primary malignant tumorApplication of paclitaxelEfflux transportersPrimary malignant tumorsUse of paclitaxelEfficacy of paclitaxelAnti-tumor effectsPeripheral solid tumorsCentral nervous systemNatural bioactive moleculesEffective anti-cancer drugsP-gp transporterVascular endothelial cellsBlood concentrationsMalignant tumorsGlioma treatmentNervous systemP-gpAnti-cancer drugsSolid tumorsTumor tissue
2022
Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review
Shen X, Jain A, Aladelokun O, Yan H, Gilbride A, Ferrucci LM, Lu L, Khan SA, Johnson CH. Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review. Frontiers In Molecular Biosciences 2022, 9: 958666. PMID: 36090030, PMCID: PMC9453556, DOI: 10.3389/fmolb.2022.958666.Peer-Reviewed Original ResearchColorectal cancerCRC patientsNarrative reviewSex steroid hormone estrogenFemale CRC patientsAnti-tumor effectsPI3K/Akt/Sex-related influencesSex-related factorsAsparagine synthetase expressionSex-specific factorsClinical outcomesTumor burdenCRC progressionPoor prognosisHormone estrogenEstrogen receptorSOX12 expressionRole of sexTherapeutic useAkt/Cancer cellsSynthetase expressionL-asparaginasePatientsA phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 (ezabenlimab) and BI 754111 in patients (pts) with advanced solid tumors.
Yamamoto N, Hafez N, Tolcher A, Teufel M, Geng J, Svensson L, Lahmar M, Gounder M. A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 (ezabenlimab) and BI 754111 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2022, 40: 3095-3095. DOI: 10.1200/jco.2022.40.16_suppl.3095.Peer-Reviewed Original ResearchDose-limiting toxicityImmune checkpoint inhibitorsDoublet combinationsCheckpoint inhibitorsPrimary endpointPhase Ia/Ib studySolid tumorsManageable safety profileMDM2-p53 antagonistsProgression-free survivalAdvanced solid tumorsBiliary tract carcinomaMetastatic solid tumorsSoft tissue sarcomasAnti-tumor effectsWild-type cancersAnti-tumor activityLogistic regression modelsPhase IaMultiple tumor typesG3 anemiaG3 neutropeniaG4 thrombocytopeniaIA/IBMurine double minuteAHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer
Park HJ, Boo S, Park I, Shin MS, Takahashi T, Takanari J, Homma K, Kang I. AHCC®, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer. Frontiers In Immunology 2022, 13: 875872. PMID: 35514996, PMCID: PMC9066372, DOI: 10.3389/fimmu.2022.875872.Peer-Reviewed Original ResearchConceptsDual immune checkpoint blockadeImmune checkpoint blockadeAnti-tumor effectsCheckpoint blockadeBearing miceStandardized extractTumor growthMC38 tumor-bearing miceGut microbiomePD-1/CTLATumor-infiltrating CD8Cell functionCancer bearing miceT cell functionKi-67 expressionImmune cell functionMurine colon cancerTumor bearing miceTumor-bearing miceTreatment of cancerTreatment strategiesT cellsTherapeutic effectGranzyme BColon cancerA randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): The Aspirin after Breast Cancer (ABC) Trial
Chen W, Ballman K, Winer E, Openshaw T, Hahn O, Briccetti F, Irvin W, Pohlmann P, Carey L, Partridge A, Weiss A, McCall L, Matyka C, Carvan M, Holmes M. A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): The Aspirin after Breast Cancer (ABC) Trial. Journal Of Clinical Oncology 2022, 40: 360922-360922. DOI: 10.1200/jco.2022.40.36_suppl.360922.Peer-Reviewed Original ResearchInvasive disease-free survivalHER2-negative breast cancerStratified hazard ratioDisease-free survivalHazard ratioBreast cancerIDFS eventsAspirin usersCardiovascular diseaseGrade 3/4 adverse eventsAspirin/non-steroidal anti-inflammatory drugsNon-steroidal anti-inflammatory drugsAdjuvant aspirin therapyRandomized phase IIIRegular aspirin usersPlacebo-controlled trialDouble-blinded fashionBreast cancer survivorsBody mass indexBreast cancer trialsBreast cancer survivalBreast cancer recurrenceMultiple epidemiologic studiesAnti-inflammatory drugsAnti-tumor effectsIn vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2
Gbyli R, Song Y, Liu W, Gao Y, Biancon G, Chandhok NS, Wang X, Fu X, Patel A, Sundaram R, Tebaldi T, Mamillapalli P, Zeidan AM, Flavell RA, Prebet T, Bindra RS, Halene S. In vivo anti-tumor effect of PARP inhibition in IDH1/2 mutant MDS/AML resistant to targeted inhibitors of mutant IDH1/2. Leukemia 2022, 36: 1313-1323. PMID: 35273342, PMCID: PMC9103411, DOI: 10.1038/s41375-022-01536-x.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaMyelodysplastic syndromeMDS/acute myeloid leukemiaRefractory acute myeloid leukemiaPARP inhibitionVivo anti-tumor effectsAlternate therapeutic optionsSubset of AMLAnti-tumor effectsPre-clinical studiesRibose polymerase inhibitorsSerial transplantation assaysHomologous recombination defectsTherapeutic optionsTreatment optionsOverall engraftmentHigh relapseIDH inhibitionMyeloid leukemiaIsocitrate dehydrogenase 1Small molecule inhibitorsCell frequencyXeno-graftsIDH1/2 mutationsMalignant transformation
2021
Agonistic CD40 Antibodies in Cancer Treatment
Djureinovic D, Wang M, Kluger HM. Agonistic CD40 Antibodies in Cancer Treatment. Cancers 2021, 13: 1302. PMID: 33804039, PMCID: PMC8000216, DOI: 10.3390/cancers13061302.Peer-Reviewed Original ResearchAgonistic CD40 antibodyCD40 antibodyDendritic cellsAntigen presentationClinical developmentEarly phase clinical trialsAgonist CD40 antibodyActivation of CD8Pro-inflammatory effectsAntigen-presenting cellsT cell functionRenal cell carcinomaAnti-tumor effectsPhase clinical trialsAnti-tumor activityT cell activationCancer Genome AtlasSystemic therapyCell carcinomaCostimulatory moleculesCD40 expressionClinical trialsPancreatic adenocarcinomaPreclinical modelsT cells
2020
CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM)
Lukas R, Chiocca E, Bush N, Landolfi J, Cavaliere R, Yu J, Kurz S, Demars N, Buck J, Hadar N, Miao J, Loewy J, Wang Y, Gelb A, Cooper L. CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM). Neuro-Oncology 2020, 22: ii39-ii39. PMCID: PMC7650356, DOI: 10.1093/neuonc/noaa215.162.Peer-Reviewed Original ResearchPD-1 inhibitorsImmune-mediated anti-tumor effectsAnti-tumor effectsRecurrent glioblastomaIL-12PD-1Overall survivalFollow-upIncreased PD-1 expressionIL-12 therapyPD-1 expressionPhase 2 trialPhase 1 trialPost-treatment biopsiesGene therapy candidateSurvival dataEndogenous cytokine productionIFN-g levelsTumor cell heterogeneityFunctional IL-12Blood-brain barrierCombination immunotherapyIT injectionSafety profileIFN-gIL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8ABC trial (A011502): A randomized phase III double-blinded placebo-controlled trial of aspirin as adjuvant therapy breast cancer.
Chen W, Winer E, Ballman K, Partridge A, Carey L, Carvan M, Matyka C, Openshaw T, Visvanathan K, Symington B, Holmes M. ABC trial (A011502): A randomized phase III double-blinded placebo-controlled trial of aspirin as adjuvant therapy breast cancer. Journal Of Clinical Oncology 2020, 38: tps600-tps600. DOI: 10.1200/jco.2020.38.15_suppl.tps600.Peer-Reviewed Original ResearchInvasive disease-free survivalAspirin usersCardiovascular diseaseBreast cancerHER2-negative breast cancer patientsBlinded placebo-controlled trialHER2-negative breast cancerNegative breast cancer patientsRandomized phase IIIRegular aspirin usersPlacebo-controlled trialDisease-free survivalHormone receptor statusDouble-blinded fashionMonths of diagnosisBreast cancer survivorsTime of presentationBody mass indexBreast cancer patientsTherapy-Breast CancerBreast cancer survivalMultiple epidemiologic studiesNegative breast cancerAnti-tumor effectsDaily aspirinA phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 and BI 754111 in patients (pts) with advanced solid tumors.
Tolcher A, Hafez N, Yamamoto N, Park J, Grempler R, Lucarelli A, Lahmar M, Wang B, Gounder M. A phase Ia/Ib, dose-escalation/expansion study of BI 907828 in combination with BI 754091 and BI 754111 in patients (pts) with advanced solid tumors. Journal Of Clinical Oncology 2020, 38: tps3660-tps3660. DOI: 10.1200/jco.2020.38.15_suppl.tps3660.Peer-Reviewed Original ResearchDose-limiting toxicityProgression-free survivalPrimary endpointSecondary endpointsPhase IbPhase Ia/Ib studySolid tumorsAnti-PD-1 antibodyMeasurable target lesionsAdvanced solid tumorsMaximum-tolerated doseFirst treatment cycleMetastatic solid tumorsAnti-LAG-3 antibodyTP53 wild-type tumorsAnti-tumor effectsWild-type cancersWild-type tumorsTP53 mutation statusLogistic regression modelsMultiple tumor typesEvaluable ptsIA/IBMurine double minutePFS ratesSurvival of subjects with recurrent glioblastoma receiving intratumoral administration of controlled IL-12 with limited exposure to dexamethasone.
Lukas R, Kurz S, Yu J, Landolfi J, Rao G, Amidei C, Buck J, Hadar N, Estupinan T, Miao J, Loewy J, Wang Y, Demars N, Gelb A, Cooper L. Survival of subjects with recurrent glioblastoma receiving intratumoral administration of controlled IL-12 with limited exposure to dexamethasone. Journal Of Clinical Oncology 2020, 38: 2564-2564. DOI: 10.1200/jco.2020.38.15_suppl.2564.Peer-Reviewed Original ResearchMedian overall survivalImpact of DexIL-12Intratumoral administrationIFN-gGrade III or IV gliomaImmune-mediated anti-tumor effectsLow-dose corticosteroidsAnti-tumor responsesSerum IL-12Time of resectionTumor response dataRecombinant IL-12Survival of subjectsAnti-tumor effectsExposure to dexamethasoneImmune system activationOverall survivalRecurrent glioblastomaIV gliomasControl edemaPreclinical modelsSafety profileInterleukin-12Historical controlsPhase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma
Kaley TJ, Panageas KS, Pentsova EI, Mellinghoff IK, Nolan C, Gavrilovic I, DeAngelis LM, Abrey LE, Holland EC, Omuro A, Lacouture ME, Ludwig E, Lassman AB. Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma. Annals Of Clinical And Translational Neurology 2020, 7: 429-436. PMID: 32293798, PMCID: PMC7187704, DOI: 10.1002/acn3.51009.Peer-Reviewed Original ResearchConceptsRecurrent malignant gliomaDose-limiting toxicityMTOR inhibitor temsirolimusMalignant gliomasAkt inhibitor perifosinePhase I clinical trialDose level 3Dose level 7Phase II doseSynergistic anti-tumor effectKarnofsky performance statusPhase I trialDeadly primary brain cancerPI3K/Akt/mTOR axisPrimary brain cancerAkt/mTOR axisAnti-tumor effectsPotential therapeutic targetMost malignant gliomasPrior therapyTemsirolimus dosePerformance statusI trialIntracerebral hemorrhageCombined therapy
2019
B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M, Leventhal J, Herold K, Meffre E, Bosenberg M, Kluger HM. B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. Journal For ImmunoTherapy Of Cancer 2019, 7: 153. PMID: 31200747, PMCID: PMC6567557, DOI: 10.1186/s40425-019-0613-1.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsB cell contentB-cell depletionAnti-tumor activityB cellsMuMT miceCell depletionAnti-PD-1 inhibitorsAnti-PD-1 responseB-cell depleting drugsTumor-infiltrating B cellsImpaired B-cell functionT cell-dependent tumor rejectionPD-1 inhibitionMC38 colon cancerB cell functionAnti-tumor effectsB-cell malignanciesMurine cancer modelsCell contentOverall survivalTumor rejectionCD20 antibodyAutoimmune disordersTumor shrinkageABC trial (A011502): A randomized phase III double-blinded placebo controlled trial of aspirin as adjuvant therapy breast cancer.
Chen W, Winer E, Ballman K, Partridge A, Carey L, Carvan M, Matyka C, Visvanathan K, Symington B, Holmes M. ABC trial (A011502): A randomized phase III double-blinded placebo controlled trial of aspirin as adjuvant therapy breast cancer. Journal Of Clinical Oncology 2019, 37: tps599-tps599. DOI: 10.1200/jco.2019.37.15_suppl.tps599.Peer-Reviewed Original ResearchInvasive disease-free survivalAspirin usersCardiovascular diseaseBreast cancerHER2-negative breast cancer patientsHER2-negative breast cancerNegative breast cancer patientsRandomized phase IIIRegular aspirin usersTrial of aspirinDisease-free survivalHormone receptor statusDouble-blinded fashionMonths of diagnosisBreast cancer survivorsTime of presentationBody mass indexBreast cancer patientsTherapy-Breast CancerBreast cancer survivalMultiple epidemiologic studiesNegative breast cancerAnti-tumor effectsDaily aspirinIDFS eventsEvaluation of controlled IL-12 as monotherapy in subjects with recurrent GBM.
Lukas R, Chiocca E, Kurz S, Yu J, Landolfi J, Rao G, Barrett J, Buck J, Demars N, Smith A, Miao J, Zhou Q, Gelb A, Cooper L. Evaluation of controlled IL-12 as monotherapy in subjects with recurrent GBM. Journal Of Clinical Oncology 2019, 37: 2053-2053. DOI: 10.1200/jco.2019.37.15_suppl.2053.Peer-Reviewed Original ResearchCytokine release syndromeT cell ratioRecurrent glioblastomaIL-12Low-dose DexOverall survivalImmune-mediated anti-tumor effectsIntratumoral injection of AdImmune systemAnti-tumor responsesImproved overall survivalResponse to immunotherapySerum IL-12Replication-incompetent adenovirusCytotoxic T cellsInjection of AdAnti-tumor effectsDay 0Impact of DexFlu-like symptomsIL-12 productionInduce IL-12Biomarkers of OSRecurrent GBMIntratumoral injection
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