2024
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024 PMID: 39561007, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelSorafenib or anthracycline‐based chemotherapy for progressive desmoid tumors
Costa P, Arora A, Fernandez Y, Yi I, Bakkila B, Tan H, Coelho P, Campoverde L, Hardy N, Bialick S, Freire A, D’Amato G, Chang Y, Mesenger J, Subhawong T, Haims A, Hurwitz M, Olino K, Turaga K, Deshpande H, Trent J. Sorafenib or anthracycline‐based chemotherapy for progressive desmoid tumors. Cancer 2024 PMID: 39543805, DOI: 10.1002/cncr.35647.Peer-Reviewed Original ResearchProgression-free survivalAnthracycline-containing regimensAnthracycline-based therapyDesmoid tumorsAdverse eventsOne-year progression-free survivalMulti-institutional retrospective analysisAnthracycline-containing regimenCommon grade 1Desmoid tumor patientsGrade 3 eventsAnthracycline-based chemotherapyHand-foot syndromeSecondary end pointsActivity of sorafenibProgressive desmoid tumorsYear of treatmentMedian TTRBaseline characteristicsTumor patientsLocal invasionTreatment responseSorafenibAnthracyclinesEnd points662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors
Mitchell S, Khan B, Payumo F, Gabriela Chiorean E, Gahvari Z, Randolph Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Schoenfeld A, Punekar S, Zhao D, Basu S, Nagorsen D. 662 A phase1 study of autologous engineered CD4+ and CD8+ T cells, HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor and a FAS41BB switch receptor in patients with solid tumors. 2024, a759-a759. DOI: 10.1136/jitc-2024-sitc2024.0662.Peer-Reviewed Original ResearchCost trends of metastatic renal cell carcinoma therapy: the impact of oral anticancer agents and immunotherapy
Forman R, Long J, Westvold S, Agnish K, McManus H, Leapman M, Hurwitz M, Spees L, Wheeler S, Gross C, Dinan M. Cost trends of metastatic renal cell carcinoma therapy: the impact of oral anticancer agents and immunotherapy. JNCI Cancer Spectrum 2024, 8: pkae067. PMID: 39133171, PMCID: PMC11376369, DOI: 10.1093/jncics/pkae067.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOral anticancer agentsOAA useAssociated with decreased adherenceRenal cell carcinomaAnticancer agentsDays of treatmentCombination therapyCell carcinomaStudy patientsInitial treatmentReal-world costsCombination groupImmunotherapyPatientsOOP costsTherapyTreatment typePercent daysPerspective of payersTreatmentClaims dataMedicare patientsAnalyzed differencesFee-for-service MedicareTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarray14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma
Moritz V, Xu W, Birch G, Meliki A, Bharadwaj M, Schindler N, Labaki C, Saliby R, Dinh K, Horst J, Sun M, Kashima S, Machaalani M, Lee G, Hurwitz M, McGregor B, Hirsch M, Shukla S, McDermott D, Signoretti S, Romee R, Choueiri T, Braun D. 14 Natural killer cells have impaired cytotoxicity in advanced renal cell carcinoma. The Oncologist 2024, 29: s7-s8. PMCID: PMC11301877, DOI: 10.1093/oncolo/oyae181.012.Peer-Reviewed Original ResearchNK cell phenotypeGene expression signaturesNK cell populationK562 target cellsNK cellsRenal cell carcinomaAdvanced ccRCCNK cell clustersLocalized ccRCCAnti-tumor activityNormal kidneyNatural killerCell carcinomaMarkers of tissue residencyAdvanced renal cell carcinomaProportion of NK cellsFunction of NK cellsExpression of cytotoxic genesTarget cellsNK cell dysfunctionTotal immune cellsNK cell subsetsCell phenotypeCell populationsCell renal cell carcinomaDevelopment of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC)
Kashima S, Gupta R, Moritz V, Sadak K, Adeniran A, Humphrey P, Dinulescu D, Palmer D, Hammond S, Bosenberg M, Hurwitz M, Kenney P, Braun D. Development of anex vivo patient-derived tumor model (PDTM) to assess the tumor microenvironment in renal cell carcinoma (RCC). The Oncologist 2024, 29: s5-s6. PMCID: PMC11301923, DOI: 10.1093/oncolo/oyae181.008.Peer-Reviewed Original ResearchRCC tumor microenvironmentPatient-derived tumor modelsRenal cell carcinomaImmune checkpoint inhibitorsT cell functionPeripheral blood mononuclear cellsEnzyme-linked immunosorbent assayTumor microenvironmentT cellsFlow cytometryTumor fragmentsIFN-gTumor modelTumor samplesCytokine productionHealthy donor peripheral blood mononuclear cellsImpact of immune checkpoint inhibitorsAnti-PD-1 monoclonal antibodyDonor peripheral blood mononuclear cellsCD4+CD25+ regulatory T cellsCD8+ T cell populationsResection of renal cell carcinomaSurgical resection of renal cell carcinomaAnti-PD-1 antibodyMetastatic renal cell carcinomaMolecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC).
Zaemes J, Hugaboom M, Shah V, Haas N, McDermott D, Jegede O, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Hurwitz M, Wu C, Einstein D, Hammers H, Signoretti S, West D, Denize T, Atkins M, Braun D. Molecular analysis of the HCRN GU16-260-Cohort A phase II study of first-line (1L) nivolumab (nivo) and salvage nivo + ipilimumab (ipi) in patients (pts) with advanced clear cell renal cell carcinoma (accRCC). Journal Of Clinical Oncology 2024, 42: 4546-4546. DOI: 10.1200/jco.2024.42.16_suppl.4546.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint blockadeProgression-free survivalProgressive diseaseAnti-VEGFOverall survivalAssociated with higher progression-free survivalTumor samplesAdvanced clear cell renal cell carcinomaCombined immune checkpoint blockadeHigher progression-free survivalIncreased PFSImmune checkpoint blockade therapyShorter progression-free survivalClear cell renal cell carcinomaAnti-VEGF therapyCell renal cell carcinomaWeeks of therapyRenal cell carcinomaBiomarkers of efficacyFFPE tumor samplesNIVO monotherapyCheckpoint blockadeDecreased OSProspective trialsInitial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors.
Thomas S, Pico B, Henick B, Leidner R, Samhouri Y, Isaacs J, Weiss J, Hurwitz M, Grewal J, Luke J, Chattopadhyay S, Wang Y, Motta M, Murray J, Barton D, Pinchasik D, MacBeath G, Moser J. Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors. Journal Of Clinical Oncology 2024, 42: 2542-2542. DOI: 10.1200/jco.2024.42.16_suppl.2542.Peer-Reviewed Original ResearchT-cell receptor-engineered T-cell therapyLoss of heterozygositySolid tumorsHLA-A*02:01HLA matchingHLA allelesPatients evaluated to dateFirst-in-human clinical trialDose level 1Dose level 3Pre-identify patientsTarget HLA alleleAntitumor T cellsT-cell therapyLoss of heterozygosity testingT-cell attackMaster protocolProportion of patientsScreening protocolCombination of HLAHLA LOHHLA lossImmunosuppressive microenvironmentMAGE-A1HLA typingAFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors.
Mitchell S, Khan B, Payumo F, Chiorean E, Gahvari Z, Hecht J, Hurwitz M, Leidner R, Lenz H, Pelster M, Punekar S, Schoenfeld A, Zhao D, Vallaster M, Nagorsen D. AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR, a CD8α/β coreceptor, and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors. Journal Of Clinical Oncology 2024, 42: tps8650-tps8650. DOI: 10.1200/jco.2024.42.16_suppl.tps8650.Peer-Reviewed Original ResearchOptimal biological doseCD8+ T cellsAutologous CD4+Advanced/metastatic solid tumorsT cellsSolid tumorsSwitch receptorsDose expansionDose escalationCD4+Transgenic TCRMechanism of actionDose-limiting toxicity observation periodRecommended phase 2 doseT cell cytotoxic activityIncreased T cell activationCD4+ T cellsHelper T cell responsesPreventing T cell exhaustionPost-treatment follow-up periodChimeric switch receptorsPhase 2 doseImmunosuppressive tumor microenvironmentT cell exhaustionDuration of responseSLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma
Wirth L, Hugaboom M, Street K, Ruthen N, Jegede O, Schindler N, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. SLAMF7+ CD8+ T cells exhibit decreased anti-tumor responses in renal cell carcinoma. The Journal Of Immunology 2024, 212: 1491_5876-1491_5876. DOI: 10.4049/jimmunol.212.supp.1491.5876.Peer-Reviewed Original ResearchCD8+ T cellsImmune-checkpoint inhibitorsRenal cell carcinomaCD8+ T-cell effector functionT cell effector functionT cellsCell carcinomaResistance to immune-checkpoint inhibitorsEffector functionsPopulation of CD8+ T cellsCD3+ T cellsTreatment of renal cell carcinomaHealthy human PBMCTumor-infiltrating lymphocytesAnti-tumor responsesPatient T cellsReduction of pro-inflammatory cytokinesAnti-tumor functionPro-inflammatory cytokinesSingle-cell transcriptome analysisNivolumab monotherapySLAMF7 expressionClinical benefitGranzyme BIFN-gTreatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A)
Atkins M, Jegede O, Haas N, Mcdermott D, Bilen M, Stein M, Sosman J, Alter R, Plimack E, Ornstein M, Hurwitz M, Peace D, Einstein D, Catalano P, Hammers H, Regan M. Treatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A). Journal For ImmunoTherapy Of Cancer 2024, 12: e008293. PMID: 38604810, PMCID: PMC11015345, DOI: 10.1136/jitc-2023-008293.Peer-Reviewed Original ResearchConceptsTreatment-free survivalInternational Metastatic RCC Database ConsortiumFavorable-risk patientsNivolumab monotherapyPhase II study of nivolumabCessation of immunotherapyFavorable-risk diseaseProtocol therapy cessationStudy of nivolumabSystemic therapy initiationTreatment naive patientsPhase II studyRenal cell carcinomaKaplan-Meier curvesActive treatment approachPartitioned survival analysisCheckMate 067Stable diseaseProtocol therapyAdvanced melanomaTherapy initiationTreatment-freeCell carcinomaClear-cellProtocol treatmentCD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma
Pal S, Tran B, Haanen J, Hurwitz M, Sacher A, Tannir N, Budde L, Harrison S, Klobuch S, Patel S, Meza L, Dequeant M, Ma A, He Q, Williams L, Keegan A, Gurary E, Dar H, Karnik S, Guo C, Heath H, Yuen R, Morrow P, Agarwal N, Srour S. CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. Cancer Discovery 2024, 14: of1-of14. PMID: 38583184, PMCID: PMC11215406, DOI: 10.1158/2159-8290.cd-24-0102.Peer-Reviewed Original ResearchClear cell renal cell carcinomaChimeric antigen receptorCAR-T cellsT-cell therapyCell renal cell carcinomaRenal cell carcinomaT cellsCell carcinomaSolid tumorsAllogeneic CAR-T cell therapyChimeric antigen receptor T cellsAdvanced clear cell renal cell carcinomaAllogeneic CAR-T cellsClinical trialsCAR-T cell productsCAR-T cell therapyTreatment of solid tumorsFirst-in-human clinical trialCAR-T constructsDose-limiting toxicityT cell productionNovel treatment optionsTreatment of clear cell renal cell carcinomaHematologic malignanciesAntigen receptorArea Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma
Rahman S, Long J, Westvold S, Leapman M, Spees L, Hurwitz M, McManus H, Gross C, Wheeler S, Dinan M. Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma. JAMA Network Open 2024, 7: e248747. PMID: 38687479, PMCID: PMC11061765, DOI: 10.1001/jamanetworkopen.2024.8747.Peer-Reviewed Original ResearchConceptsMetastatic renal cell carcinomaArea-level measuresRenal cell carcinomaPatient-level factorsSystemic therapyEthnic disparitiesRelative risk ratiosSocially vulnerable areasCell carcinomaMeasures of social vulnerabilityMedicare beneficiariesCohort studyFee-for-service Medicare Parts AOdds ratioReceipt of systemic therapyLogistic regressionArea-level characteristicsAssociated with lack of treatmentNon-Hispanic blacksRetrospective cohort studyIndividual-level demographicsNon-Hispanic whitesAssociated with disparitiesUS Medicare beneficiariesMeasures of disadvantageProviding 0.1 Full-Time Equivalent (FTE) Support to Fellowship Core Faculty Improves Faculty Involvement in Fellowship Education and Recruitment
Butt A, Christian J, Kress A, Lu B, Hurwitz M, Goldberg S, Podoltsev N, Gilkes L, Lee A. Providing 0.1 Full-Time Equivalent (FTE) Support to Fellowship Core Faculty Improves Faculty Involvement in Fellowship Education and Recruitment. Journal Of Cancer Education 2024, 39: 325-334. PMID: 38430454, DOI: 10.1007/s13187-024-02414-z.Peer-Reviewed Original ResearchFull-time equivalent supportFull-time equivalentAmerican Council for Graduate Medical EducationCore facultyFellowship programsFellowship educationGraduate Medical EducationImprove job satisfactionCF programPotential unintended consequencesMedical educationSalary supportSurvey respondentsIncreased participationMedical oncologyUnintended consequencesSubspecialty fellowshipsIncreased senseSense of commitmentJob satisfactionFellowshipEducationFaculty involvementA0305 Pathologic gleason upgrading following high-resolution micro-ultrasound, conventional ultrasound and MRI fusion biopsy techniques: A comparative study
Lokeshwar S, Choksi A, Smani S, Kong V, Sundaresan V, Brito J, Renzulli J, Sprenkle P, Michael M. A0305 Pathologic gleason upgrading following high-resolution micro-ultrasound, conventional ultrasound and MRI fusion biopsy techniques: A comparative study. European Urology 2024, 85: s1101. DOI: 10.1016/s0302-2838(24)00884-4.Peer-Reviewed Original Research
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 analysis542 TIGIT as a potential therapeutic target in renal cell carcinoma
Kashima S, Soulati H, Madsen K, Sadak K, Wirth L, Hurwitz M, Kluger H, Sznol M, Humphrey P, Adeniran A, Kenney P, Braun D. 542 TIGIT as a potential therapeutic target in renal cell carcinoma. 2023, a616-a616. DOI: 10.1136/jitc-2023-sitc2023.0542.Peer-Reviewed Original Research1017 SLAMF7+ CD8+ exhausted T cell-specific gene signature is associated with resistance to PD1 blockade in renal cell carcinoma
Hugaboom M, Street K, Ruthen N, Wirth L, Jegede O, Schindler N, McDermott D, Plimack E, Sosman J, Haas N, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. 1017 SLAMF7+ CD8+ exhausted T cell-specific gene signature is associated with resistance to PD1 blockade in renal cell carcinoma. 2023, a1125-a1125. DOI: 10.1136/jitc-2023-sitc2023.1017.Peer-Reviewed Original ResearchTotal and treatment-related costs of care associated with in patients with metastatic renal cell carcinoma receiving targeted or immune therapy.
Rahman S, Long J, Westvold S, Wheeler S, Spees L, Leapman M, Hurwitz M, McManus H, Gross C, Dinan M. Total and treatment-related costs of care associated with in patients with metastatic renal cell carcinoma receiving targeted or immune therapy. JCO Oncology Practice 2023, 19: 28-28. DOI: 10.1200/op.2023.19.11_suppl.28.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOral anticancer agentsInitial treatmentRetrospective cohort studyUse of immunotherapyYear of diagnosisRenal cell carcinomaDirect treatment costsMean Medicare paymentsMedicare paymentsMedicare Part DInitial therapyCohort studyMetastatic diagnosisCell carcinomaCombination therapyImmunotherapyMedicare beneficiariesPatientsAge 65Disease controlOlder ageStudy periodTherapyDiagnosis