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
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
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 function
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
Role 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
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 Research
2011
Future 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