2025
HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang Q, Braun D, Clauser K, Ramesh V, Shirole N, Duke-Cohan J, Nabilsi N, Kramer N, Forman C, Lippincott I, Klaeger S, Phulphagar K, Chea V, Kim N, Vanasse A, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani E, Stevens J, Lane W, Camp S, Meli K, Pappalardi M, Herbert Z, Qiu X, Cejas P, Long H, Shukla S, Van Allen E, Choueiri T, Churchman L, Abelin J, Gurer C, MacBeath G, Childs R, Carr S, Keskin D, Wu C, Kaelin W. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell 2025, 188: 1807-1827.e34. PMID: 40023154, PMCID: PMC11988688, DOI: 10.1016/j.cell.2025.01.046.Peer-Reviewed Original ResearchClear cell renal cell carcinomaCancer immunotherapyAntigen-specific T cell responsesAllogeneic stem cell transplantationEndogenous retrovirusesClear cell renal cell carcinoma patientsLow mutational burdenCell renal cell carcinomaStem cell transplantationT cell responsesRenal cell carcinomaVHL tumor suppressor geneTumor suppressor geneHLA-bound peptidesEndogenous retrovirus expressionNon-ccRCCCell transplantationMutational burdenSpontaneous regressionCell carcinomaT cellsCase reportSuppressor geneHIF transcription factorsImmunotherapy
2023
First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC)
Autio K, Higano C, Nordquist L, Appleman L, Zhang T, Zhu X, Babiker H, Vogelzang N, Prasad S, Schweizer M, Madan R, Billotte S, Cavazos N, Bogg O, Li R, Chan K, Cho H, Kaneda M, Wang I, Zheng J, Tang S, Hollingsworth R, Kern K, Petrylak D. First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Journal For ImmunoTherapy Of Cancer 2023, 11: e005702. PMID: 36948505, PMCID: PMC10040068, DOI: 10.1136/jitc-2022-005702.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerAndrogen deprivation therapyRadiographic progression-free survivalCastration-resistant prostate cancerPhase 1 studyBiochemical recurrenceProstate cancerImmunotherapy regimenMedian durationDose escalationMedian radiographic progression-free survivalAntigen-specific T cell responsesImmune-related adverse eventsRecommended phase 2 doseSpecific T cell responsesPhase 2 doseImmune checkpoint inhibitorsModest antitumor activityObjective response rateProgression-free survivalAntigen-specific immunityT cell responsesInfluenza-like illnessSignificant side effectsDeprivation therapy
2022
A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer.
Runcie K, Dallos M, Khan S, Gray J, Marco P, Ping L, LaTourette D, Anderson C, Spina C, Yu J, Deutsch I, Sheeri S, Gutierrez A, Stein M. A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer. Journal Of Clinical Oncology 2022, 40: tps5115-tps5115. DOI: 10.1200/jco.2022.40.16_suppl.tps5115.Peer-Reviewed Original ResearchAndrogen deprivation therapyProstate-specific antigenTumor-associated antigensBiochemical recurrenceProstate cancerRadiation therapyTumor microenvironmentRadical prostatectomyStudy treatmentPromote anti-tumor immune responsesAntigen-specific T cell responsesBiochemical recurrence of prostate cancerBiochemically recurrent prostate cancerCastration sensitive prostate cancerPSA responseTime to PSA progressionDose of study treatmentAnti-tumor immune responseStandard first-line treatmentEvidence of metastatic diseaseMyeloid-derived suppressor cellsImmunosuppressive regulatory T cellsPeptide antigensLive-attenuated Listeria monocytogenesRecurrent prostate cancer
2020
LTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA
Reardon D, Brem S, Desai A, Bagley S, Kurz S, De La Fuente M, Nagpal S, Welch M, Hormigo A, Forsyth P, Mandell J, Khagi S, Aiken R, Walbert T, Lieberman F, Portnow J, Batiste J, Carroll N, Sylvester A, Campbell P, Lowy I, Dolgoter A, Boyer J, Kraynyak K, Morrow M, McMullan T, Weiner D, Skolnik J. LTBK-01. INO-5401 AND INO-9012 DELIVERED INTRAMUSCULARLY (IM) WITH ELECTROPORATION (EP) IN COMBINATION WITH CEMIPLIMAB (REGN2810) IN NEWLY DIAGNOSED GLIOBLASTOMA. Neuro-Oncology 2020, 22: ii237-ii237. PMCID: PMC7678727, DOI: 10.1093/neuonc/noaa215.988.Peer-Reviewed Original ResearchCohort AMedian OSAntigen-specific T cell responsesImmune responseRobust systemic immune responsesInterferon-gamma ELISPOTDiagnosed GBM patientsT cell responsesEncoding tumor antigensAdverse event profileNewly diagnosed glioblastomaPeripheral immune responseSystemic immune responsesCheckpoint inhibitionPD-1Diagnosed GBMDiagnosed glioblastomaOverall survivalCohort B.Tumor antigensCD8+T cellsMedian agePrimary endpointCohort BEvent profileStaphylococcus aureus α-toxin suppresses antigen-specific T cell responses
Lee B, Olaniyi R, Kwiecinski JM, Wardenburg JB. Staphylococcus aureus α-toxin suppresses antigen-specific T cell responses. Journal Of Clinical Investigation 2020, 130: 1122-1127. PMID: 31873074, PMCID: PMC7269593, DOI: 10.1172/jci130728.Peer-Reviewed Original ResearchConceptsT cell responsesSkin infectionsCell responsesAntigen-specific T cell responsesOVA-specific T cell responsesT cell-mediated immunityS. aureusΑ-toxinAntigen-specific modelChicken egg OVACell-mediated immunityT cell memoryAntigen-specific memoryPrimary skin infectionsInvasive staphylococcal diseaseStaphylococcus aureus α-toxinDevelopment of immunityΑ-toxin expressionAureus α-toxinProtective immunityInvasive infectionsLeading causeLoss of DCsStaphylococcal diseaseLong-term protection
2019
Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablation
2016
Quantifying in vivo murine antigen-specific T cell responses without requirement for prior knowledge of antigen identity
Kibbi N, Hong E, Ezaldein H, Hanlon D, Fahmy T, Edelson R. Quantifying in vivo murine antigen-specific T cell responses without requirement for prior knowledge of antigen identity. Transfusion And Apheresis Science 2016, 56: 179-189. PMID: 28007431, DOI: 10.1016/j.transci.2016.11.004.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaExtracorporeal photochemotherapyCalcium fluxT cellsAntigen-specific T cell responsesMalignant cellsPatient-specific tumor antigensOVA-specific T cellsAntigen-specific T cellsAntigen-specific T cell activationControl recipient micePeptide-loaded DCImmune-based therapiesAnti-tumor responseT cell responsesAnti-cancer immunotherapyT-cell lymphomaT cell engagementT cell activationT cell receptor engagementPatient-specific responsesAdoptive transferClinical responseLymph nodesPeripheral bloodArtificial bacterial biomimetic nanoparticles synergize pathogen-associated molecular patterns for vaccine efficacy
Siefert AL, Caplan MJ, Fahmy TM. Artificial bacterial biomimetic nanoparticles synergize pathogen-associated molecular patterns for vaccine efficacy. Biomaterials 2016, 97: 85-96. PMID: 27162077, PMCID: PMC5999034, DOI: 10.1016/j.biomaterials.2016.03.039.Peer-Reviewed Original ResearchConceptsMonophosphoryl lipid APathogen-associated molecular patternsT cell responsesToll-like receptorsAntigen-specific T-helper 1Antigen-specific T cell responsesCell responsesMolecular patternsAntibody-mediated responsesT helper 1Model antigen ovalbuminBacterial pathogen-associated molecular patternsCytokine profileAntigen-loaded nanoparticlesTLR ligandsCellular immunityHelper 1Vaccine efficacyAntigen ovalbuminVaccine platformImmune responseNanoparticulate vaccinesLipid AOvalbuminCpG
2015
Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity*
Hong E, Usiskin IM, Bergamaschi C, Hanlon DJ, Edelson RL, Justesen S, Pavlakis GN, Flavell RA, Fahmy TM. Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity*. Journal Of Biological Chemistry 2015, 291: 8931-8950. PMID: 26719339, PMCID: PMC4861462, DOI: 10.1074/jbc.m115.695304.Peer-Reviewed Original ResearchConceptsT cell responsesArtificial antigen-presenting cellsDendritic cellsIL-15Antigen-presenting cellsIL-15RαCell responsesAntigen-specific T cell responsesAntigen-processing dendritic cellsMaximal T cell responsesAnti-tumor immunitySame dendritic cellOptimal immune responseIL-15 functionsMechanism of actionIL-2Antigen deliveryImmune responseDC surfaceParacrine fashionTumor progressionMurine melanomaCellular mechanismsAggressive modelEnhanced potency
2013
SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer
Dhodapkar KM, Gettinger SN, Das R, Zebroski H, Dhodapkar MV. SOX2-specific adaptive immunity and response to immunotherapy in non-small cell lung cancer. OncoImmunology 2013, 2: e25205. PMID: 24073380, PMCID: PMC3782159, DOI: 10.4161/onci.25205.Peer-Reviewed Original ResearchNon-small cell lung carcinomaT cell responsesTumor-associated antigensClinical responseNSCLC patientsDisease regressionT cellsAnti-PD-1 monoclonal antibodyAntigen-specific T cell responsesNon-small cell lung cancerPD-1-blocking antibodiesPeripheral blood mononuclear cellsDeath-1 receptorImmune checkpoint blockadeCell lung cancerBlood mononuclear cellsLung cancer patientsCell lung carcinomaImportant tumor-associated antigenMajor oncogenic driverIntramolecular epitopeCheckpoint blockadeImmunotherapeutic strategiesTumor immunityHumoral responseThe development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164)
Kuerten S, Schickel A, Kerkloh C, Recks M, Addicks K, Ruddle N, Lehmann P. The development of tertiary lymphoid organs in the central nervous system facilitates determinant spreading of the MP4-specific T cell response (P4164). The Journal Of Immunology 2013, 190: 172.9-172.9. DOI: 10.4049/jimmunol.190.supp.172.9.Peer-Reviewed Original ResearchTertiary lymphoid organsT cell responsesCentral nervous systemExperimental autoimmune encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisCell responsesLymphoid organsNervous systemFormation of TLOsAntigen-specific T cell responsesSecondary progressive multiple sclerosisHuman autoimmune disease multiple sclerosisAutoimmune disease multiple sclerosisT cell compartmentalizationB cell aggregatesChronic disease stageDisease multiple sclerosisSevere clinical diseaseHigh endothelial venulesGerminal center formationMyelin basic proteinAutoimmune encephalomyelitisCNS autoimmunityCortical pathology
2002
Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection
Suresh M, Lanier G, Large MK, Whitmire JK, Altman JD, Ruddle NH, Ahmed R. Role of Lymphotoxin α in T-Cell Responses during an Acute Viral Infection. Journal Of Virology 2002, 76: 3943-3951. PMID: 11907234, PMCID: PMC136110, DOI: 10.1128/jvi.76.8.3943-3951.2002.Peer-Reviewed Original ResearchConceptsT cell responsesCD8 T cellsLymphocytic choriomeningitis virusT cellsT cell activationLymphoid architectureMajor histocompatibility complex class I tetramersVirus-specific CD8 T cell responsesLCMV-specific CD8 T cellsLCMV-specific T-cell responsesVirus-specific CD8 T cellsAntigen-specific T cell responsesCD8 T cell responsesLCMV-specific T cellsT cell-mediated immunopathologyLTalpha-deficient miceClass I tetramersAcute viral infectionCD4 T cellsAdoptive transfer experimentsCell transfer experimentsLCMV clearanceNonlymphoid organsAdoptive transferAcute infection
2000
Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. Journal Of Clinical Investigation 2000, 105: 967-976. PMID: 10749576, PMCID: PMC377485, DOI: 10.1172/jci8970.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmino Acid SequenceCell DivisionCells, CulturedCross ReactionsEpitopes, T-LymphocyteFemaleGlatiramer AcetateHumansImmunodominant EpitopesImmunosuppressive AgentsInterferon-gammaInterleukin-5Leukocytes, MononuclearLigandsMaleMiddle AgedMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin SheathPeptide FragmentsPeptidesTetanus ToxoidTh2 CellsConceptsT cell responsesMultiple sclerosisGlatiramer acetateT cellsAntigen-specific T cell responsesTh2-polarized immune responseCross-reactive T cellsAlters immune functionHuman autoimmune diseasesAcetate inducesCross-reactive responsesT cell receptorT cell linesImmune deviationMost patientsTh2 typeAutoimmune disordersTh2 cytokinesAutoimmune diseasesDaily injectionsIL-13IL-5Th2 cellsHealthy subjectsImmune response
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