2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysis
2022
Maximizing the value of phase III trials in immuno-oncology: A checklist from the Society for Immunotherapy of Cancer (SITC)
Atkins MB, Abu-Sbeih H, Ascierto PA, Bishop MR, Chen DS, Dhodapkar M, Emens LA, Ernstoff MS, Ferris RL, Greten TF, Gulley JL, Herbst RS, Humphrey RW, Larkin J, Margolin KA, Mazzarella L, Ramalingam SS, Regan MM, Rini BI, Sznol M. Maximizing the value of phase III trials in immuno-oncology: A checklist from the Society for Immunotherapy of Cancer (SITC). Journal For ImmunoTherapy Of Cancer 2022, 10: e005413. PMID: 36175037, PMCID: PMC9528604, DOI: 10.1136/jitc-2022-005413.Peer-Reviewed Original ResearchConceptsPhase III trialsImmunotherapy of cancerIII trialsCurative responseImmune checkpoint inhibitor monotherapyCell death protein 1Checkpoint inhibitor monotherapyDefinitive predictive biomarkersDurable clinical benefitProgression-free survivalMinority of patientsDeath protein 1Variety of indicationsClinical trial designAnimal tumor modelsLimited Phase IDrug development programsImmunotherapy combinationsInvestigational chemotherapyImmunotherapy fieldInhibitor monotherapyOverall survivalDismal prognosisClinical benefitSurvival outcomes
2021
Resistance mechanisms to checkpoint inhibitors
Weiss SA, Sznol M. Resistance mechanisms to checkpoint inhibitors. Current Opinion In Immunology 2021, 69: 47-55. PMID: 33676271, DOI: 10.1016/j.coi.2021.02.001.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsPD-1/PD-L1 axisMultiple immune checkpoint inhibitorsPD1/PD-L1PD-L1 axisHuman translational studiesPre-clinical studiesPre-clinical animalResistance mechanismsCheckpoint inhibitorsPD-L1Clinical outcomesTreatment failureClinical trialsTranslational studiesCancer treatmentPotential mechanismsInhibitorsPatientsClinicTrialsAntibodies
2020
Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy
Sharma M, Khong H, Fa’ak F, Bentebibel SE, Janssen LME, Chesson BC, Creasy CA, Forget MA, Kahn LMS, Pazdrak B, Karki B, Hailemichael Y, Singh M, Vianden C, Vennam S, Bharadwaj U, Tweardy DJ, Haymaker C, Bernatchez C, Huang S, Rajapakshe K, Coarfa C, Hurwitz ME, Sznol M, Hwu P, Hoch U, Addepalli M, Charych DH, Zalevsky J, Diab A, Overwijk WW. Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy. Nature Communications 2020, 11: 661. PMID: 32005826, PMCID: PMC6994577, DOI: 10.1038/s41467-020-14471-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCarcinoma, Renal CellCD8-Positive T-LymphocytesCohort StudiesDrug Therapy, CombinationFemaleHumansInterferon-gammaInterleukin-2IpilimumabLymphocyte ActivationMelanomaMiceMice, Inbred C57BLPolyethylene GlycolsProdrugsReceptors, Interleukin-2T-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaConceptsNKTR-214Interleukin-2Treg depletionT cellsHigh-dose interleukin-2Suppressive regulatory T cellsSuperior anti-tumor activityAnti-tumor CD8Dose interleukin-2Peptide-based vaccinationRegulatory T cellsCheckpoint blockade therapyTreatment-associated toxicityIL-2 pathwayRenal cell carcinomaAnti-tumor activityAnti-cancer therapyMechanism of actionTreg dynamicsIntratumoral TregsBlockade therapyCytokines IFNCell carcinomaMetastatic melanomaTherapeutic impact
2019
Immunotherapy of Melanoma: Facts and Hopes
Weiss SA, Wolchok JD, Sznol M. Immunotherapy of Melanoma: Facts and Hopes. Clinical Cancer Research 2019, 25: 5191-5201. PMID: 30923036, PMCID: PMC6726509, DOI: 10.1158/1078-0432.ccr-18-1550.Peer-Reviewed Original ResearchConceptsOverall survivalMetastatic diseaseImmune therapyPredictive biomarkersNivolumab/ipilimumab combinationRandomized phase III trialLong-term clinical benefitImmunobiology of tumorsDuration of therapyPhase III trialsLong-term survivorsEffective immune therapyAdjuvant settingIpilimumab combinationMetastatic settingIII trialsPatient subsetsClinical benefitImmune modulationMetastatic melanomaClinical trialsSingle agentTherapyTrue increaseCell therapy
2018
Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3
Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, Zheng L, Zhou T, Badri T, Yao S, Zhu S, Boto A, Sznol M, Melero I, Vignali DAA, Schalper K, Chen L. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell 2018, 176: 334-347.e12. PMID: 30580966, PMCID: PMC6365968, DOI: 10.1016/j.cell.2018.11.010.Peer-Reviewed Original ResearchConceptsFibrinogen-like protein 1MHC-IILAG-3Major histocompatibility complex class IILymphocyte activation gene-3Histocompatibility complex class IILiver-secreted proteinsImmune inhibitory receptorsProtein 1Immune evasion mechanismsCell immunityTumor immunityPoor prognosisCancer immunotherapyCancer patientsInhibitory receptorsEvasion mechanismsHuman cancer cellsCell activationClass IIMouse tumorsMonoclonal antibodiesCancer cellsInhibitory ligandsInhibitory functionCollateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 2018, 67: dbi180002. PMID: 29937434, PMCID: PMC6054443, DOI: 10.2337/dbi18-0002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalAutoimmune DiseasesB7-H1 AntigenDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseGenotypeHLA-DR4 AntigenHumansHypoglycemic AgentsInsulinInsulin SecretionIsoantibodiesKetosisModels, ImmunologicalNeoplasmsPancreasPancreatitisProgrammed Cell Death 1 ReceptorConceptsInsulin-dependent diabetesCheckpoint inhibitorsAdverse eventsHLA-DR4Classic type 1 diabetesPD-L1 checkpoint inhibitorsEvidence of pancreatitisImmune adverse eventsSolid organ cancersType 1 diabetesPeridiagnosis periodPositive autoantibodiesL1 antibodyInsulin-DependentHigh riskPatientsDiabetesCancerInhibitorsKetoacidosisAutoimmuneAutoantibodiesPancreatitisComplicationsSyndromeCombination Strategies PD-1/PD-L1 Antagonists
Sznol M. Combination Strategies PD-1/PD-L1 Antagonists. The Cancer Journal 2018, 24: 54-57. PMID: 29360729, DOI: 10.1097/ppo.0000000000000304.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 antagonistsPD-L1 antagonistsClinical antitumor activityEarly clinical developmentClinical trial designOptimal combination partnersSuboptimal responsePromising regimensCombination partnersMechanisms of resistanceCombination trialsClinical progressIndividual patientsOptimal doseBiomarker strategiesTrial designClinical developmentOverall outcomeAntagonistPatientsPrior exposureAntitumor activityRegimensAgentsInnate
2017
Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer
Zloza A, Karolina Palucka A, Coussens LM, Gotwals PJ, Headley MB, Jaffee EM, Lund AW, Sharpe AH, Sznol M, Wainwright DA, Wong KK, Bosenberg MW. Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer. Journal For ImmunoTherapy Of Cancer 2017, 5: 77. PMID: 28923102, PMCID: PMC5604351, DOI: 10.1186/s40425-017-0278-6.Peer-Reviewed Original ResearchConceptsImmunotherapy of cancerCancer immunologyHumanized modelImmunotherapy researchImmune-targeted therapiesAntitumor immune responseCancer immunotherapy researchCancer immunotherapyImmune responseMurine modelMouse modelImmunotherapyPredictive valueSubsequent panel discussionNational HarborAnnual MeetingImmunologyDrug developmentCancerMiceFuture directionsImmunocompetentTherapyCancer modeling
2015
Cancer Immunotherapy: Past Progress and Future Directions
Atkins MB, Sznol M. Cancer Immunotherapy: Past Progress and Future Directions. Seminars In Oncology 2015, 42: 518-522. PMID: 26320057, DOI: 10.1053/j.seminoncol.2015.05.001.Peer-Reviewed Original ResearchTherapeutic Combinations of Immune-Modulating Antibodies in Melanoma and Beyond
Cohen J, Sznol M. Therapeutic Combinations of Immune-Modulating Antibodies in Melanoma and Beyond. Seminars In Oncology 2015, 42: 488-494. PMID: 25965368, DOI: 10.1053/j.seminoncol.2015.02.014.Peer-Reviewed Original ResearchConceptsImmune modulating antibodiesCheckpoint inhibitorsMetastatic renal cell carcinomaPD-1/PD-L1 antagonistsSelection of patientsPD-L1 antagonistsRenal cell carcinomaNumber of malignanciesAutoimmune toxicityCell carcinomaCombination therapyMetastatic melanomaTherapeutic combinationsSingle agentCostimulatory agentsOptimal outcomesAntibodiesPatientsMalignancyPromising activityMelanomaFuture combinationInhibitorsCarcinomaAgonistsRole of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis
Ma B, Herzog EL, Lee CG, Peng X, Lee CM, Chen X, Rockwell S, Koo JS, Kluger H, Herbst RS, Sznol M, Elias JA. Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis. Cancer Research 2015, 75: 487-496. PMID: 25511377, PMCID: PMC4321965, DOI: 10.1158/0008-5472.can-13-3339.Peer-Reviewed Original ResearchConceptsMelanoma lung metastasisPulmonary melanoma metastasesPulmonary metastasesLung metastasesMelanoma metastasesGenetic deletionBreast cancer cellsPlexin C1 receptorsPulmonary microenvironmentPoor prognosisSemaphorin 7AMelanoma spreadChitinase 3MetastasisCHI3L1Cancer progressionSema7AInhibitory wayCancer cellsReceptorsSignificant reductionΒ1 integrinNovel pathwayCritical roleIL13Rα2
2014
Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy
Sznol M. Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy. The Cancer Journal 2014, 20: 290-295. PMID: 25098290, DOI: 10.1097/ppo.0000000000000056.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 blockadePD-L1 blockadeT cell responsesTumor-specific T-cell responsesB7-H1/PDCell responsesOverall risk-benefit ratioAntitumor T-cell responsesTumor microenvironmentAnimal tumor model systemsAbundant preclinical dataAutoimmune-like toxicitiesSubset of patientsRecent clinical trialsRisk-benefit ratioT lymphocyte suppressionEarly clinical developmentActivated T lymphocytesTumor model systemsCombination anticancer therapyClinical responseDurable responsesDeath-1Metastatic melanomaPreclinical data
2012
Chitinase-like Proteins in Lung Injury, Repair, and Metastasis
Lee CG, Dela Cruz CS, Ma B, Ahangari F, Zhou Y, Halaban R, Sznol M, Elias JA. Chitinase-like Proteins in Lung Injury, Repair, and Metastasis. Annals Of The American Thoracic Society 2012, 9: 57-61. PMID: 22550243, PMCID: PMC3359113, DOI: 10.1513/pats.201112-056ms.Peer-Reviewed Original ResearchAdvances in the Treatment of Metastatic Melanoma: New Immunomodulatory Agents
Sznol M. Advances in the Treatment of Metastatic Melanoma: New Immunomodulatory Agents. Seminars In Oncology 2012, 39: 192-203. PMID: 22484191, DOI: 10.1053/j.seminoncol.2012.01.007.Peer-Reviewed Original ResearchConceptsNew immunomodulatory agentsImmunomodulatory agentsMetastatic melanomaT cell activationT cellsAdverse eventsDendritic cellsClinical activityOngoing phase III trialsRandomized phase III studyCo-inhibitory receptor PD-1Co-stimulatory antibodiesMajor adverse eventsPhase III studyPhase III trialsReceptor PD-1Durable clinical responsesImmune cell subsetsSubsequent clinical trialsParticular T cellsActivated T cellsMechanism of actionAdvanced diseaseClinical responseIII study
2011
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy.
Flies DB, Sandler BJ, Sznol M, Chen L. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. The Yale Journal Of Biology And Medicine 2011, 84: 409-21. PMID: 22180678, PMCID: PMC3238327.Peer-Reviewed Original ResearchConceptsB7-H1/PDTumor-associated antigensImmune responseCancer immunotherapyMolecular pathwaysCancer-specific immune responsesImmune-mediated destructionSpecific immune responseCancer immunotherapy researchAnti-cancer effectsCoinhibitory functionImmunotherapeutic modalitiesCoinhibitory moleculesClinical evidenceImmunotherapy researchMalignant diseaseNew immunotherapeuticsImmune cellsImmune functionStromal cellsCancerMonoclonal antibodiesCancer cellsImmunotherapyCurrent knowledgeWhite Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy
Weber J, Atkins M, Hwu P, Radvanyi L, Sznol M, Yee C, Committee O. White Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy. Clinical Cancer Research 2011, 17: 1664-1673. PMID: 21325070, DOI: 10.1158/1078-0432.ccr-10-2272.Peer-Reviewed Original ResearchConceptsAdoptive T-cell therapyTumor-infiltrating lymphocytesAdoptive cell therapyInterleukin-2TIL therapyClinical trialsRandomized phase II/III clinical trialsExpansion of TILTumor antigen-specific T cellsHigh-dose IL-2Phase II/III clinical trialsHigh-dose interleukin-2Autologous tumor-infiltrating lymphocytesLonger progression-free survivalPhase II/IIIAntigen-specific T cellsCell therapyT cell-based therapiesTIL infusion productsClinical response rateNonrandomized clinical trialProgression-free survivalStage IV melanomaMetastatic melanoma patientsT-cell therapyFuture perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th2010"
Ascierto PA, De Maio E, Bertuzzi S, Palmieri G, Halaban R, Hendrix M, Kashani-sabet M, Ferrone S, Wang E, Cochran A, Rivoltini L, Lee PP, Fox BA, Kirkwood JM, Ullmann CD, Lehmann FF, Sznol M, Schwartzentruber DJ, Maio M, Flaherty K, Galon J, Ribas A, Yang J, Stroncek DF, Mozzillo N, Marincola FM. Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th2010". Journal Of Translational Medicine 2011, 9: 32. PMID: 21439082, PMCID: PMC3078100, DOI: 10.1186/1479-5876-9-32.Peer-Reviewed Original Research
2010
Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies
Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical Experiences With Anti-CD137 and Anti-PD1 Therapeutic Antibodies. Seminars In Oncology 2010, 37: 508-516. PMID: 21074066, DOI: 10.1053/j.seminoncol.2010.09.008.Peer-Reviewed Original ResearchConceptsDurable objective responsesPotent cellular immunityAnti-CD137 antibodyCellular immune responsesLigand PD-L1Reasonable safety profileSevere liver toxicityTumor response criteriaTransplantable murine tumorsDose-dependent effectSurface of antigenImmunostimulatory mAbsAntitumor immunityObjective responseDeath-1PD-L1Tumor immunityCellular immunitySafety profileLiver toxicityClinical activityT lymphocytesImmune responseTumor antigensAgonist antibody
2005
Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation
Thamm DH, Kurzman ID, King I, Li Z, Sznol M, Dubielzig RR, Vail DM, MacEwen EG. Systemic Administration of an Attenuated, Tumor-Targeting Salmonella typhimurium to Dogs with Spontaneous Neoplasia: Phase I Evaluation. Clinical Cancer Research 2005, 11: 4827-4834. PMID: 16000580, DOI: 10.1158/1078-0432.ccr-04-2510.Peer-Reviewed Original ResearchConceptsAntitumor responseTumor tissueAntitumor activityMajor antitumor responsesTumor-bearing dogsDose-limiting toxicityInherent antitumor activitySignificant antitumor activityRefractory feverDisease stabilizationEscalation trialFirst infusionShort-term toxicityIncisional biopsyClinicopathologic variablesSystemic administrationTumor targeting capacityMalignant tumorsAcute deathSpontaneous tumorsSpontaneous neoplasiaPowerful anticancer therapySalmonella typhimuriumVital signsPhase I