2022
Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure
Qu R, Kluger Y, Yang J, Zhao J, Hafler D, Krause D, Bersenev A, Bosenberg M, Hurwitz M, Lucca L, Kluger H. Longitudinal single-cell analysis of a patient receiving adoptive cell therapy reveals potential mechanisms of treatment failure. Molecular Cancer 2022, 21: 219. PMID: 36514045, PMCID: PMC9749221, DOI: 10.1186/s12943-022-01688-5.Peer-Reviewed Original ResearchConceptsAdoptive cell therapySingle-cell analysisDepth single-cell analysisSingle-cell RNAACT productsDisease progressionT-cell receptor sequencingCell therapyFamily genesFeatures of exhaustionMultiple tumor typesCell expansionGenesNew clonotypesTIL preparationsClonal cell expansionCytokine therapyTreatment failureSerial bloodClonesEffector functionsSerial samplesTumor typesCellular therapyTherapy
2021
Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Larkin J, Sarnaik A, Chesney J, Khushalani N, Kirkwood J, Weber J, Lewis K, Medina T, Kluger H, Thomas S, Domingo-Musibay E, Olah J, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Shi W, Wu R, Fardis M, Hamid O. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. Journal Of Clinical Oncology 2021, 39: 9505-9505. DOI: 10.1200/jco.2021.39.15_suppl.9505.Peer-Reviewed Original ResearchAnti-PD-1 therapyPrior anti-PD-1 therapyObjective response rateImmune checkpoint inhibitorsAdvanced melanomaPrimary resistanceAnti-PD-1 resistanceAnti-PD-1 responseBaseline tumor burdenDays of cyclophosphamideDays of fludarabineMedian cumulative durationMedian prior linesLong-term followAdoptive cell therapyStandard of careDetection of progressionNew safety risksDuration of exposureAutologous tumorMelanoma progressPrior therapyRECIST 1.1TIL productionCheckpoint inhibitorsLifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma
Sarnaik AA, Hamid O, Khushalani NI, Lewis KD, Medina T, Kluger HM, Thomas SS, Domingo-Musibay E, Pavlick AC, Whitman ED, Martin-Algarra S, Corrie P, Curti BD, Oláh J, Lutzky J, Weber JS, Larkin JMG, Shi W, Takamura T, Jagasia M, Qin H, Wu X, Chartier C, Finckenstein F, Fardis M, Kirkwood JM, Chesney JA. Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma. Journal Of Clinical Oncology 2021, 39: 2656-2666. PMID: 33979178, PMCID: PMC8376325, DOI: 10.1200/jco.21.00612.Peer-Reviewed Original ResearchConceptsObjective response rateDisease control rateAdvanced melanomaPrimary refractoryControl rateMetastatic melanomaTreatment optionsInterleukin-2Investigator-assessed objective response rateHigh-dose interleukin-2Tumor-Infiltrating Lymphocyte TherapyImmune checkpoint inhibitorsPrimary end pointTumor-infiltrating lymphocytesEffective treatment optionLimited treatment optionsAdoptive cell therapyMajor unmet needLymphodepletion regimenPrior therapyCheckpoint inhibitorsAdverse eventsDurable responsesMedian durationPartial response
2020
Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.
Sarnaik A, Khushalani N, Chesney J, Lewis K, Medina T, Kluger H, Thomas S, Domingo Musibay E, Pavlick A, Whitman E, Martin-Algarra S, Corrie P, Lutzky J, Hamid O, Wu R, Shi W, Fardis M, Weber J, Larkin J, Kirkwood J. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. Journal Of Clinical Oncology 2020, 38: 10006-10006. DOI: 10.1200/jco.2020.38.15_suppl.10006.Peer-Reviewed Original ResearchBRAF/MEK inhibitorsMultiple prior therapiesMedian DoRPrior therapyCheckpoint inhibitorsAdvanced melanomaMelanoma patientsMedian studyMEK inhibitorsBaseline tumor burdenCohort 2 patientsIL-2 regimensAdverse event profileLong-term followMetastatic melanoma patientsIL-2 dosesAdoptive cell therapyUnresectable metastatic melanomaBaseline disease burdenBody's natural defensesAnti-cancer therapyAutologous tumorRECIST v1.1TIL productionAdvanced disease
2019
Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1.
Sarnaik A, Khushalani N, Chesney J, Kluger H, Curti B, Lewis K, Thomas S, Whitman E, Hamid O, Lutzky J, Pavlick A, Weber J, Larkin J, Barton D, Yung L, Suzuki S, Fardis M, Kirkwood J. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1. Journal Of Clinical Oncology 2019, 37: 2518-2518. DOI: 10.1200/jco.2019.37.15_suppl.2518.Peer-Reviewed Original ResearchBRAF/MEK inhibitorsTumor-infiltrating lymphocytesMetastatic melanoma patientsMelanoma patientsTIL therapyPrior therapyAdvanced metastatic melanoma patientsDurable long-term responsesMEK inhibitorsBaseline tumor burdenCohort 2 patientsMultiple prior therapiesTIL infusion productsIL-2 dosesAdoptive cell therapyUnresectable metastatic melanomaBaseline disease burdenOverall disease controlAutologous tumorTIL infusionTIL productionMedian followCheckpoint inhibitorsUnresectable melanomaAdverse eventsSafety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy.
Sarnaik A, Thomas S, Davar D, Kirkwood J, Kluger H, Lutzky J, Wilson M, Pavlick A, Curti B, Whitman E, Phan G, Ernstoff M, Takamura K, Barton D, Suzuki S, Karyampudi L, Samberg N, Fardis M, Chesney J. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy. Journal Of Clinical Oncology 2019, 37: 136-136. DOI: 10.1200/jco.2019.37.8_suppl.136.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesBRAF/MEK inhibitorsMetastatic melanoma patientsMetastatic melanomaPrior therapyCheckpoint inhibitorsMelanoma patientsIL-2Advanced metastatic melanoma patientsHigh-dose IL-2MEK inhibitorsBaseline tumor burdenCohort 2 patientsDose IL-2Frequency of AEsPrior systemic therapyAdoptive cell therapyUnresectable metastatic melanomaPreliminary dataAutologous tumorLymphodepletion regimenTIL treatmentMedian followProgressive diseaseComplete response
2017
Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy.
Sarnaik A, Kluger H, Chesney J, Sethuraman J, Veerapathran A, Simpson-Abelson M, Lotze M, Larsen B, Fischkoff S, Suzuki S, Wang L, Mirgoli M, Fardis M, Curti B. Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 3045-3045. DOI: 10.1200/jco.2017.35.15_suppl.3045.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesAdvanced metastatic melanomaMetastatic melanomaTIL productsPrior therapySafety profileIL-2Advanced metastatic melanoma patientsNon-hematologic grade 3Cell therapyPrior systemic therapyAcceptable safety profilePhase 2 studyMetastatic melanoma patientsAdoptive cell therapyEx vivo expansionEnlisted patientsRECIST 1.1Study patientsCheckpoint therapyMedian durationSurgical resectionSystemic therapyAutologous lymphocytesMedian age
2014
NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma
Giesen E, Jilaveanu LB, Parisi F, Kluger Y, Camp RL, Kluger HM. NY-ESO-1 as a potential immunotherapeutic target in renal cell carcinoma. Oncotarget 2014, 5: 5209-5217. PMID: 24970819, PMCID: PMC4170640, DOI: 10.18632/oncotarget.2101.Peer-Reviewed Original ResearchConceptsNY-ESO-1 expressionNY-ESO-1Renal cell carcinomaCell carcinomaMetastatic sitesRenal tissueCancer-testis antigen NY-ESO-1Antigen NY-ESO-1Adjacent normal renal tissuesClear cell renal cell carcinomaRCC specimensMetastatic RCC specimensPapillary renal cell carcinomaCell renal cell carcinomaPotential immunotherapeutic targetAdoptive cell therapySubset of RCCTumor-specific antigensClear cell carcinomaNovel immune therapiesPrimary RCC specimensBenign renal tissueNormal renal tissueDifferent tumor sitesImmune therapy
2013
Advances in the systemic treatment of metastatic melanoma.
Yushak M, Kluger HM, Sznol M. Advances in the systemic treatment of metastatic melanoma. Oncology 2013, 27: 374-81. PMID: 25184258, PMCID: PMC6092183.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalDrug Therapy, CombinationHumansImidazolesImmunologic FactorsImmunotherapy, AdoptiveIndolesIpilimumabMelanomaMutationNivolumabOximesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesSkin NeoplasmsSulfonamidesVemurafenibConceptsMetastatic melanomaTumor-host immune interactionsRandomized phase III trialPhase III trialsCombination of dabrafenibAdoptive cell therapyStandard of carePromising new agentPhase II dataIII trialsOverall survivalSystemic treatmentPredictive biomarkersMechanisms of resistanceTreatment outcomesIndividual patientsLimited efficacyAvailable agentsImmune interactionsNew agentsMolecular alterationsEffective agentCell therapyCurrent agentsMelanoma cells