2025
Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses
Lakshmipathi J, Santha S, Li M, Qian Y, Roy S, Luheshi N, Politi K, Bosenberg M, Eyles J, Muthusamy V. Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses. Cancer Immunology, Immunotherapy 2025, 74: 250. PMID: 40560386, PMCID: PMC12198101, DOI: 10.1007/s00262-025-04105-0.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseTumor-associated macrophagesCytotoxic T cellsImmune responseActivity of checkpoint inhibitorsAnti-PD-L1 antibodyPhagocytosis of tumor cellsAnti-PD-L1Enhanced anti-tumorAntigen presentation machineryCell-based immune responsesMurine tumor modelsTh1-type cytokinesColorectal carcinoma tumorsICI resistanceMurine IL12Checkpoint inhibitorsPresentation machineryIntratumoral deliveryResistant tumorsAdvanced diseaseCarcinoma tumorsTumor microenvironmentMurine tumorsT cellsSelective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500
Appleman V, Matsuda A, Ganno M, Zhang D, Rosentrater E, Lopez A, Porciuncula A, Hatten T, Christensen C, Merrigan S, Lee H, Lee M, Wang C, Dong L, Huang J, Iartchouk N, Wang J, Xu H, Yoneyama T, Piatkov K, Haridas S, Harbison C, Gregory R, Parent A, Lineberry N, Arendt C, Schalper K, Abu-Yousif A. Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500. Cancer Immunology Research 2025, 13: 661-679. PMID: 39918395, PMCID: PMC12046323, DOI: 10.1158/2326-6066.cir-24-0103.Peer-Reviewed Original ResearchIntratumoral myeloid cellsMyeloid cellsTumor microenvironmentImmune responseCCR2+ cellsI interferonImmunosuppressive myeloid populationsImmune activation in vitroImmune cell markersLocal immune activationMurine tumor modelsAdaptive immune responsesAntibody drug conjugatesType I interferonAntitumor immunityInnate immune responseMyeloid populationsSTING agonistsSolid tumorsCCR2 proteinImmune activationTumor modelCell markersHuman tumorsAdaptive immunity
2024
Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma
Santana J, Shewarega A, Nam D, Duncan J, Madoff D, Hyder F, Coman D, Chapiro J. Molecular MRI of T-cell immune response to cryoablation in immunologically hot vs. cold hepatocellular carcinoma. JHEP Reports 2024, 7: 101294. PMID: 40028344, PMCID: PMC11870164, DOI: 10.1016/j.jhepr.2024.101294.Peer-Reviewed Original ResearchT cell infiltrationHepatocellular carcinomaRadiological-pathological correlationImaging mass cytometryImmune responseT1-weighted MRITumor-infiltrating CD8+ T lymphocytesAnti-tumor immune responseCD8+ T lymphocytesIncreased T lymphocyte infiltrationImaging biomarkersNon-immunogenic tumorsSystemic lymph nodesT lymphocyte infiltrationMurine tumor modelsImmune cell typesLocal tumor therapyPrimary liver cancerNon-invasive imaging biomarkerTesla MRI scannerInduce liver cirrhosisImmunogenic tumorsLocoregional therapySystemic immunotherapyHCC lesions
2022
CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor
Prokhnevska N, Cardenas M, Valanparambil R, Sobierajska E, Barwick B, Jansen C, Reyes Moon A, Gregorova P, delBalzo L, Greenwald R, Bilen M, Alemozaffar M, Joshi S, Cimmino C, Larsen C, Master V, Sanda M, Kissick H. CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 2022, 56: 107-124.e5. PMID: 36580918, PMCID: PMC10266440, DOI: 10.1016/j.immuni.2022.12.002.Peer-Reviewed Original ResearchConceptsTumor-draining lymph nodesCD8<sup>+</sup> T cell activationT cell activationCD8<sup>+</sup> T cellsStem-like cellsT cellsCell activationEffector differentiationLymph nodesTumor-specific CD8<sup>+</sup> T cellsActivated CD8<sup>+</sup> T cellsAnti-tumor T cell responsesTumor-draining lymph node cellsCD8+ T cell activationCo-stimulationT cell responsesAntigen-presenting cellsMurine tumor modelsResponse to cancerEffector phenotypeTumor immunotherapyTumor modelTumorCell responsesAcute viruses
2019
1375TiP Pembrolizumab (pembro) plus lenvatinib (len) for first-line treatment of patients (pts) with advanced melanoma: Phase III LEAP-003 study
Eggermont A, Carlino M, Hauschild A, Ascierto P, Arance A, Daud A, O’Day S, Taylor M, Smith A, Rodgers A, Moreno B, Diede S, Kluger H. 1375TiP Pembrolizumab (pembro) plus lenvatinib (len) for first-line treatment of patients (pts) with advanced melanoma: Phase III LEAP-003 study. Annals Of Oncology 2019, 30: v561. DOI: 10.1093/annonc/mdz255.063.Peer-Reviewed Original ResearchBlinded independent central reviewPD-1 inhibitorsAdvanced melanomaSanofi GenzymeSubsidiary of MerckArray BioPharmaDohme Corp.Pierre FabreRoche-GenentechEnd pointMerck SharpBaseline tumor samplesNCI CTCAE v4.0Performance status 0/1Antitumor activityPrimary end pointSecondary end pointsFirst-line standardFirst-line treatmentUntreated stage IIIIndependent central reviewMurine tumor modelsPDGF receptor αEligible ptsQd po
2018
B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction
Chen L, Azuma T, Yu W, Zheng X, Luo L, Chen L. B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 3126-3131. PMID: 29507197, PMCID: PMC5866601, DOI: 10.1073/pnas.1722043115.Peer-Reviewed Original ResearchConceptsB7-H1 expressionDendritic cellsT cell responsesB7-H1CTL responsesTumor escapeB7-H1/PDCell responsesSubdominant T-cell responsesPolyclonal T cell responsesCombination cancer immunotherapyDifferent dendritic cellsAdaptive resistanceT lymphocyte destructionAdvanced human cancersMurine tumor modelsSurvival benefitTumor AgDominant AgAntibody blockadeCancer immunotherapyDC functionImmune destructionLymphocyte destructionT lymphocytes
2016
Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells
Moreno B, Zaretsky JM, Garcia-Diaz A, Tsoi J, Parisi G, Robert L, Meeth K, Ndoye A, Bosenberg M, Weeraratna AT, Graeber TG, Comin-Anduix B, Hu-Lieskovan S, Ribas A. Response to Programmed Cell Death-1 Blockade in a Murine Melanoma Syngeneic Model Requires Costimulation, CD4, and CD8 T Cells. Cancer Immunology Research 2016, 4: 845-857. PMID: 27589875, PMCID: PMC5050168, DOI: 10.1158/2326-6066.cir-16-0060.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorDendritic CellsInterferon-gammaLymphocytes, Tumor-InfiltratingMacrophagesMelanomaMice, Inbred C57BLMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins B-rafXenograft Model Antitumor AssaysConceptsPD-1 blockade therapyPD-1 blockadeCD8 T cellsBlockade therapyDendritic cellsT cellsTumor modelEffector T cell functionSyngeneic murine tumor modelsAntitumor activityPD-L1 expressionT cell primingImmune cell recruitmentT cell functionTumor-associated macrophagesMurine tumor modelsTumor-host interactionsStrong antitumor activityCD80/86 costimulationL1 therapyInflammatory profileClinical benefitMHC-IIPeripheral tissuesCell recruitment
2007
A phase 1 dynamic accelerated titration dose escalation study of the vascular disrupting agent NPI-2358
Spear M, LoRusso P, Tolcher A, Lin C, Wang D, Heath E, Lloyd G, Cropp G, Papadopoulos K. A phase 1 dynamic accelerated titration dose escalation study of the vascular disrupting agent NPI-2358. Journal Of Clinical Oncology 2007, 25: 14097-14097. DOI: 10.1200/jco.2007.25.18_suppl.14097.Peer-Reviewed Original ResearchStable diseaseAdverse eventsDrug accumulationGrade 2 adverse eventsMultiple murine tumor modelsDose-escalation studyDose-limiting toxicityObserved adverse eventsPhase 1 studyTumor vascular endothelial cellsDirect cytotoxic activityMurine tumor modelsVascular endothelial cellsTumor vascular collapseEscalation studyFirst doseDose escalationSafety profileEfficacious dosePreclinical dataTumor regressionPancreatic adenocarcinomaAverage CmaxVascular collapsePK data
2006
A phase I dose escalation trial of ispinesib (SB-715992) administered days 1–3 of a 21-day cycle in patients with advanced solid tumors
Heath E, Alousi A, Eder J, Valdivieso M, Vasist L, Appleman L, Bhargava P, Colevas A, Lorusso P, Shapiro G. A phase I dose escalation trial of ispinesib (SB-715992) administered days 1–3 of a 21-day cycle in patients with advanced solid tumors. Journal Of Clinical Oncology 2006, 24: 2026-2026. DOI: 10.1200/jco.2006.24.18_suppl.2026.Peer-Reviewed Original ResearchGrade 4 neutropeniaAdvanced solid tumorsDose levelsDay 1Phosphohistone 3Solid tumorsGrade 3 febrile neutropeniaMultiple murine tumor modelsGrade 1 fatigueGrade 3 neutropeniaToxicity of myelosuppressionGrade 3/4 toxicitiesSerial tumor biopsiesRenal cell carcinomaMurine tumor modelsKinesin spindle proteinPreliminary pharmacokinetic dataSignificant antitumor activityNovel cytotoxic agentsEvaluable patientsFebrile neutropeniaMTD cohortStable diseaseEscalation trialCell carcinoma
2005
A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer
Murren J, Modiano M, Kummar S, Clairmont C, Egorin M, Chu E, Sznol M. A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer. Investigational New Drugs 2005, 23: 123-135. PMID: 15744588, DOI: 10.1007/s10637-005-5857-6.Peer-Reviewed Original ResearchConceptsPhase II trialDose levelsII trialVNP40101MGrade 2 adverse eventsIntra-patient dose escalationPre-treated patient populationBroad anti-tumor activityGrade 3 thrombocytopeniaPhase I trialPeak plasma concentrationDose-related toxicityMurine tumor modelsAnti-tumor activityModerate granulocytopeniaAcute headacheStarting doseAdverse eventsI trialMajor toxicityDose escalationFacial flushingPatient populationPlasma concentrationsMetastatic cancer
1987
Phase I trial of tiazofurin administered by i.v. bolus daily for 5 days, with pharmacokinetic evaluation.
Roberts JD, Stewart JA, McCormack JJ, Krakoff IR, Culham CA, Hartshorn JN, Newman RA, Haugh LD, Young JA. Phase I trial of tiazofurin administered by i.v. bolus daily for 5 days, with pharmacokinetic evaluation. Journal Of The National Cancer Institute 1987, 71: 141-9. PMID: 3802111.Peer-Reviewed Original ResearchConceptsTreatment interruptionTransient toxic effectsM2/dayTreatment coursePhase I clinical trialToxic effectsAntitumor activityPhase II trialPhase I trialBolus IV infusionFrequent treatment interruptionsSerum biochemical abnormalitiesSystemic toxic effectsCoadministration of allopurinolMurine tumor modelsUric acid productionLow dose levelsSignificant antitumor activityBolus dailyInjury manifestTransient pericarditisII trialSerum hemoglobinI trialIV infusion
1981
Multimodal treatment of primary breast carcinoma Analysis of accomplishments and problem areas
Weiss R, Henney J, DeVita V. Multimodal treatment of primary breast carcinoma Analysis of accomplishments and problem areas. The American Journal Of Medicine 1981, 70: 844-851. PMID: 7011024, DOI: 10.1016/0002-9343(81)90541-6.Peer-Reviewed Original ResearchConceptsAxillary nodesInvolved axillary nodesDisease-free survivalUse of chemotherapyBreast carcinoma patientsCertain patient groupsFuture clinical trialsPrimary breast carcinomaBetter therapeutic indexMurine tumor modelsCarcinoma patientsDrug regimensMultimodal treatmentPatient groupClinical trialsBreast carcinomaBreast cancerTherapeutic indexChemotherapy modePatientsSpecific subgroupsTumor modelMastectomyChemotherapyHuman subjects
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