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 model662 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 ResearchTIGIT 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 microarrayDevelopment 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 carcinomaAFNT-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-gCD70-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 receptor
2022
558 CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the phase 1 COBALT-RCC study
Pal S, Tran B, Haanen J, Hurwitz M, Sacher A, Agarwal N, Tannir N, Budde E, Harrison S, Klobuch S, Patel S, Dequeant M, Karsten V, Cohen K, Gurary E, Dar H, Ma A, Sharma A, Srour S. 558 CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the phase 1 COBALT-RCC study. 2022, a584-a584. DOI: 10.1136/jitc-2022-sitc2022.0558.Peer-Reviewed Original Research
2017
A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors.
Diab A, Tannir N, Bernatchez C, Haymaker C, Bentebibel S, Curti B, Wong M, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Aung S, Imperiale M, Cho D, Tykodi S, Puzanov I, Kluger H, Hurwitz M, Hwu P, Sznol M. A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2017, 35: e14040-e14040. DOI: 10.1200/jco.2017.35.15_suppl.e14040.Peer-Reviewed Original ResearchNKTR-214Phase 1/2 studyT cellsIL-2 receptor pathwayTumor immune cell infiltratesTumor microenvironmentNivolumab combination therapyDose limiting toxicitiesImmune cell infiltratesUnconfirmed complete responseMetastatic solid tumorsWeeks of treatmentFavorable safety profileIL-2 pathwayIL-2 cytokineT-cell clonalityBiomarker dataTumor response dataImmunotherapy-naïveMonotherapy trialsQ3w scheduleRECIST 1.1Checkpoint inhibitorsEffector CD8Adverse eventsEffect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma.
Hurwitz M, Diab A, Bernatchez C, Haymaker C, Kluger H, Tetzlaff M, Gergel I, Tagliaferri M, Imperiale M, Aung S, Hoch U, Zalevsky J, Hwu P, Sznol M, Tannir N. Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma. Journal Of Clinical Oncology 2017, 35: 454-454. DOI: 10.1200/jco.2017.35.6_suppl.454.Peer-Reviewed Original ResearchNKTR-214T cellsTumor microenvironmentIL-2 receptor pathwayAnti-PD-1 blockadeAdvanced renal cell carcinomaImmune-related AEPatient experienced DLTPrior TKI treatmentImmune checkpoint inhibitorsT-cell receptor diversityAdvanced solid tumorsPD-1 expressionT-cell infiltratesActivity of CD8Effector T cellsFavorable safety profileRenal cell carcinomaAnti-tumor activityBaseline CD8Experienced DLTsLow TILsRECIST 1.1Checkpoint inhibitorsEffector CD8
2016
Changes in T cell immunity in patients with metastatic castration resistant prostate treated with Radium-223 treatment.
Kim J, Kang Y, Shin M, Deshpande H, Hurwitz M, Roberts J, Cardinale J, Narayana A, Kang I, Petrylak D. Changes in T cell immunity in patients with metastatic castration resistant prostate treated with Radium-223 treatment. Journal Of Clinical Oncology 2016, 34: 295-295. DOI: 10.1200/jco.2016.34.2_suppl.295.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPeripheral blood mononuclear cellsT cell immunityT cellsCell immunityOsseous metastasesMetastatic castration-resistant prostateCastration-resistant prostate cancerIL-7 receptor alpha chainRadium-223 treatmentEffector memory CD8PD-1 expressionEffector T cellsDeath protein 1Resistant prostate cancerCastration-resistant prostateBlood mononuclear cellsFollowing time pointsCocktail of antibodiesHost immune systemReceptor alpha chainCalcium mimeticEligible patientsEM CD8Median PSA