2023
Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Renauer P, Park J, Bai M, Acosta A, Lee W, Lin G, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function. Cancer Immunology Research 2023, 11: 1068-1084. PMID: 37253111, PMCID: PMC10527769, DOI: 10.1158/2326-6066.cir-22-0565.Peer-Reviewed Original ResearchConceptsCAR T cellsHER2-specific CAR T cellsT cellsTumor microenvironmentChimeric antigen receptor T cellsT cell-based immunotherapyAntigen receptor T cellsCD19-specific chimeric antigen receptor (CAR) T cellsCAR T-cell therapyCell-based immunotherapyReceptor T cellsT-cell therapyVivo colorectal cancer modelsColorectal cancer modelT cell functionT cell metabolismTumor infiltrationEvasion mechanismsImmunosuppressive metaboliteImmune evasionCancer modelImmunologic analysisCD19-specificUnfavorable tumor microenvironmentPDK1 deficiencyAnti-tumor Efficacy of CD19 CAR-T in a Raji B Cell Xenografted Mouse Model
Xiao Q, Su X. Anti-tumor Efficacy of CD19 CAR-T in a Raji B Cell Xenografted Mouse Model. Bio-protocol 2023, 13: e4655. PMID: 37113332, PMCID: PMC10127058, DOI: 10.21769/bioprotoc.4655.Peer-Reviewed Original ResearchCAR T cellsCD19 CAR T cellsRefractory B-cell malignanciesCell-induced tumorsChimeric antigen receptorImmune-deficient miceAnti-tumor efficacyB-cell malignanciesMouse xenograft modelTumor-killing abilityXenografted mouse modelCAR-TsT therapyHealthy donorsCD19-CARMouse modelXenograft modelTumor growthPreclinical researchTumor cellsCancer treatmentAntigen receptorMiceCellsMalignancyCost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Adults with Relapsed or Refractory Follicular Lymphoma
Potnis K, Di M, Isufi I, Gowda L, Seropian S, Foss F, Forman H, Huntington S. Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Adults with Relapsed or Refractory Follicular Lymphoma. Blood Advances 2023, 7: 801-810. PMID: 36342852, PMCID: PMC10011202, DOI: 10.1182/bloodadvances.2022008097.Peer-Reviewed Original ResearchConceptsCAR T-cell therapyT-cell therapyQuality-adjusted life yearsIncremental cost-effectiveness ratioCAR T cellsChimeric antigen receptor T-cell therapySOC therapyFollicular lymphomaT cellsLife yearsR FLRefractory follicular lymphomaT cell strategiesThird-line settingLines of therapyIncremental clinical benefitUS payer perspectiveCost-effectiveness ratioTherapy remissionUnselected patientsCare therapyClinical benefitClinical trialsTreatment strategiesPayer perspective
2022
Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors
Chen Q, Lu L, Ma W. Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors. Cancers 2022, 14: 5983. PMID: 36497465, PMCID: PMC9739567, DOI: 10.3390/cancers14235983.Peer-Reviewed Original ResearchCAR T-cell therapyT-cell therapyCAR T cellsT cellsSolid tumorsChimeric antigen receptor T-cell therapyAdequate T-cell responsesCytokine release syndromeHalf of patientsT cell responsesTumor antigen targetsRelease syndromeAdoptive immunotherapyClinical efficacyHeterogeneous solid tumorsHematological malignanciesSide effectsTarget antigenAntigen targetsTherapyTumorsCancer treatmentNon-cancer cellsCancer cellsEfficacyTher-O-02 The COBALT-LYM study of CTX130: a phase 1 dose escalation study of CD70-targeted allogeneic CRISPR-Cas9–engineered CAR T cells in patients with relapsed/refractory (R/R) T-cell malignancies
Zain, Iyer S, Sica R, Ho P, Hu B, Prica A, Weng W, Kim Y, Khodadoust, Palomba M, Foss F, Tipton K, Cullingford E, Horwitz S, Sharma A, Horwitz S. Ther-O-02 The COBALT-LYM study of CTX130: a phase 1 dose escalation study of CD70-targeted allogeneic CRISPR-Cas9–engineered CAR T cells in patients with relapsed/refractory (R/R) T-cell malignancies. European Journal Of Cancer 2022, 173: s21. DOI: 10.1016/s0959-8049(22)00591-3.Peer-Reviewed Original ResearchS262: THE COBALT‐LYM STUDY OF CTX130: A PHASE 1 DOSE ESCALATION STUDY OF CD70‐TARGETED ALLOGENEIC CRISPR‐CAS9–ENGINEERED CAR T CELLS IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) T‐CELL MALIGNANCIES
Iyer S, Sica R, Ho P, Hu B, Zain J, Prica A, Weng W, Kim Y, Khodadoust M, Palomba M, Foss F, Tipton K, Cullingford E, He Q, Sharma A, Horwitz S. S262: THE COBALT‐LYM STUDY OF CTX130: A PHASE 1 DOSE ESCALATION STUDY OF CD70‐TARGETED ALLOGENEIC CRISPR‐CAS9–ENGINEERED CAR T CELLS IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) T‐CELL MALIGNANCIES. HemaSphere 2022, 6: 163-164. DOI: 10.1097/01.hs9.0000843940.96598.e2.Peer-Reviewed Original ResearchAlloantigen-specific Chimeric Antigen Receptor Regulatory T cell therapy in non-human primate islet transplantation
Ellis G, Coker K, Winn D, Deng M, Shukla D, Bhoj V, Milone M, Wang W, Liu C, Naji A, Duran-Struuck R, Riley J. Alloantigen-specific Chimeric Antigen Receptor Regulatory T cell therapy in non-human primate islet transplantation. The Journal Of Immunology 2022, 208: 175.21-175.21. DOI: 10.4049/jimmunol.208.supp.175.21.Peer-Reviewed Original ResearchCAR-TregsLarge animal modelPeripheral bloodIslet transplantationT cellsAnimal modelsRegulatory T cell therapyArtificial antigen presenting cellsCAR-Treg therapyEffector T cellsT-cell therapyAntigen presenting cellsOptimization of therapyType 1 diabetesCAR T cellsExpanded TregsTreg therapyAdoptive transferGraft rejectionAdoptive therapyDiabetic recipientsImmunosuppressive agentsNegative recipientsTreatment of cancerBlood glucoseA genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screensSoluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies
Glez-Vaz J, Azpilikueta A, Olivera I, Cirella A, Teijeira A, Ochoa MC, Alvarez M, Eguren-Santamaria I, Luri-Rey C, Rodriguez-Ruiz ME, Nie X, Chen L, Guedan S, Sanmamed M, Gracia J, Melero I. Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies. Journal For ImmunoTherapy Of Cancer 2022, 10: e003532. PMID: 35236742, PMCID: PMC8896037, DOI: 10.1136/jitc-2021-003532.Peer-Reviewed Original ResearchConceptsMouse CD8 T cellsCD8 T cellsChimeric antigen receptorT cellsCD137 costimulationHuman CD137Surface expressionAnti-CD137 monoclonal antibodiesCAR-transduced T cellsCostimulatory molecule CD137Sequential plasma samplesCAR T cellsBasis of efficacyMouse tumor modelsProtein expression levelsCD137 agonistsSoluble CD137First patientSyngeneic tumorsAgonist agentsPharmacodynamic biomarkersClinical trialsPlasma concentrationsDynamic biomarkersSCD137Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy
Hu L, Chen L, Xiao Z, Zheng X, Chen Y, Xian N, Cho C, Luo L, Huang G, Chen L. Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy. JCI Insight 2022, 7: e148247. PMID: 34905507, PMCID: PMC8855794, DOI: 10.1172/jci.insight.148247.Peer-Reviewed Original ResearchConceptsPD-1HT cellsAdoptive immunotherapyT cell-mediated immune responsesT-cell adoptive immunotherapyAdoptive T-cell therapyCell-mediated immune responsesTumor-infiltrating CD8Antitumor activityT-cell therapySyngeneic mouse tumorsCAR T cellsDeath-1 homologExperimental tumor modelsAdoptive transferActivated CD8Coinhibitory moleculesCytokine productionDeficient miceImmune responseHuman xenograftsCD8Tumor microenvironmentTumor modelMouse tumors
2021
Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors
Liu Y, Liu G, Wang J, Zheng ZY, Jia L, Rui W, Huang D, Zhou ZX, Zhou L, Wu X, Lin S, Zhao X, Lin X. Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors. Science Translational Medicine 2021, 13 PMID: 33762437, DOI: 10.1126/scitranslmed.abb5191.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell receptorSolid tumorsChimeric antigen receptor T-cell therapyMultiple solid tumor modelsRefractory solid tumorsT-cell therapyDurable disease controlHigh response rateSynthetic T cell receptorsB-cell malignanciesHigh antigen sensitivitySolid tumor modelsAntigen recognition domainClinical benefitAntigen stimulationTumor relapseLimited efficacyAntigen sensitivityAntitumor effectsCell malignanciesResponse rateNotable toxicityTumor modelDisease control
2020
Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma
Hegde M, Joseph SK, Pashankar F, DeRenzo C, Sanber K, Navai S, Byrd TT, Hicks J, Xu ML, Gerken C, Kalra M, Robertson C, Zhang H, Shree A, Mehta B, Dakhova O, Salsman VS, Grilley B, Gee A, Dotti G, Heslop HE, Brenner MK, Wels WS, Gottschalk S, Ahmed N. Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma. Nature Communications 2020, 11: 3549. PMID: 32669548, PMCID: PMC7363864, DOI: 10.1038/s41467-020-17175-8.Peer-Reviewed Original ResearchConceptsHER2-CAR T cellsCAR T cellsT-cell infusionCAR T-cell infusionT cellsMetastatic rhabdomyosarcomaOngoing phase I trialPhase I trialT cell receptorSecond remissionI trialSerum autoantibodiesImmune reactivityDetectable diseaseTumor responseBone marrowResponse consolidationInfusionRhabdomyosarcomaImmunodominant clonesLymphodepletionRemissionPathway proteinsDiseaseMonthsLow toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant
Fabrizio VA, Kernan NA, Boulad F, Cancio M, Allen J, Higman M, Margossian SP, Mauguen A, Prockop S, Scaradavou A, Shah N, Spitzer B, Stieglitz E, Yeager N, O’Reilly R, Brentjens RJ, Jan Boelens J, Curran KJ. Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant. Bone Marrow Transplantation 2020, 55: 2160-2169. PMID: 32390002, PMCID: PMC7606268, DOI: 10.1038/s41409-020-0926-1.Peer-Reviewed Original ResearchConceptsCAR T cellsAllo-HSCTT cellsCumulative incidenceCell transplantAllogeneic hematopoietic stem cell transplantAllogeneic hematopoietic cell transplantHematopoietic stem cell transplantCAR T-cell therapyConsolidative allo-HSCTHematopoietic cell transplantYoung adult patientsFavorable overall survivalStem cell transplantT-cell therapyFavorable OSOverall survivalAdult patientsSevere toxicitySmall cohortDisease controlPatientsCD34IncidenceRelapseImaging Chimeric Antigen Receptor (CAR) Activation
Libby KA, Su X. Imaging Chimeric Antigen Receptor (CAR) Activation. Methods In Molecular Biology 2020, 2111: 153-160. PMID: 31933206, DOI: 10.1007/978-1-0716-0266-9_13.Peer-Reviewed Original Research
2019
Allogeneic CD34-Selected HSCT Following CAR T-Cells Is Associated with Low TRM and Favorable OS in Pediatric/Young Adult Patients with Relapsed/Refractory B-ALL
Fabrizio V, Boulad F, Cancio M, Higman M, Margossian S, Mauguen A, Prockop S, Scaradavou A, Shah N, Spitzer B, Yeager N, Kernan N, O'Reilly R, Boelens J, Curran K. Allogeneic CD34-Selected HSCT Following CAR T-Cells Is Associated with Low TRM and Favorable OS in Pediatric/Young Adult Patients with Relapsed/Refractory B-ALL. Blood 2019, 134: 4582. DOI: 10.1182/blood-2019-121767.Peer-Reviewed Original ResearchTransplant-related mortalityCAR T cellsB-cell acute lymphoblastic leukemiaCAR T-cell therapyAllo-HSCTYoung adult patientsComplete remissionT-cell therapyOverall survivalT cellsCumulative incidenceCalcineurin inhibitorsPlatelet engraftmentAdult patientsLate relapseMedian timeGraft sourceEntire cohortRefractory B-cell acute lymphoblastic leukemiaLess transplant-related mortalityLower transplant-related mortalityMRD-negative complete remissionChimeric antigen receptor T cellsCAR T-cell infusionAntigen receptor T cells
2018
Novel BAFF-R CAR T-Cell Therapy for CD19 Antigen-Loss Relapsed B Cell Tumors
Qin H, Dong Z, Wang X, Cheng W, Smith D, Song J, Aldoss I, Muschen M, Forman S, Kwak L. Novel BAFF-R CAR T-Cell Therapy for CD19 Antigen-Loss Relapsed B Cell Tumors. Blood 2018, 132: 1411. DOI: 10.1182/blood-2018-99-117513.Peer-Reviewed Original ResearchCD19 CAR T cellsCAR T cellsCAR T-cell therapyT-cell therapyBAFF-R expressionT cellsB-cell malignanciesAntigen lossB-cell tumorsCell malignanciesClonal B-cell tumorChimeric antigen receptor T cellsAntigen receptor T cellsSame donorCD22 CAR T cellsSurface stainingCD19 antigen lossLoss of CD19Degranulation marker CD107aCells/mouseProgressive tumor growthIFN-γ productionReceptor T cellsSame healthy donorsPatient-derived xenografts
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