grant
Project 4: Awakening immune responses to GBM by enhancing immune cell trafficking and activation with oHSV armed with Cetuximab-CCL5 and anti-CD47 antibody payloads.
Organization BRIGHAM AND WOMEN'S HOSPITALLocation BOSTON, UNITED STATESPosted 7 Feb 2013Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025Ab-dependent cellular cytotoxicityAdenosineAdoptive Cell TransfersAnti-CD47Anti-EGFR Monoclonal AntibodyAnti-Epidermal Growth Factor Receptor Monoclonal AntibodyAntibodiesBindingBiodistributionBiological MarkersBody TissuesBrainBrain CancerBrain Nervous SystemC-C CKR-1C-C Chemokine Receptor Type 1CAR T cellsCAR modified T cellsCAR-TCAR-TsCC chemokine receptor 1CC-CKR-1CCL5CCR-1CCR1CCR1 geneCCR1 receptorsCD47CD47 AntigenCD47 GlycoproteinCD47 geneCKR-1CMKBR1CMKR1CMKR1 GeneCancersCell BodyCell Communication and SignalingCell SignalingCellsCetuximabChemokine (C-C Motif) Ligand 5Chemokine (C-C Motif) Receptor 1Chemotactic CytokinesCirculationCitiesClinicalClinical Treatment MoabClinical TrialsCombined Modality TherapyCytotoxic cellD17S136EDataDevelopmentDoseEGF ReceptorEGFRERBB ProteinEatingEncephalonEngineeringEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsFc ReceptorFood IntakeFutureGlioblastomaGoalsGood Manufacturing ProcessGood manufacturing practiceGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaGrowth AgentsGrowth FactorGrowth SubstancesHER1HM145HSV-1HSV1Herpes SimplexHerpes Simplex InfectionsHerpes Simplex Type 1Herpes Simplex Virus 1Herpes Simplex Virus Type 1Herpes simplex diseaseHerpesvirus 1Herpesvirus hominis diseaseHomologous Chemotactic CytokinesHumanIgG1ImmuneImmune infiltratesImmune mediated therapyImmune responseImmunesImmunityImmunocompetentImmunologic StimulationImmunological StimulationImmunologically Directed TherapyImmunomodulationImmunostimulationImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyIn VitroInflammatoryIntegrin-Associated ProteinIntercrinesIntracellular Communication and SignalingInvestigational DrugsInvestigational New DrugsInvestmentsK lymphocyteLD78 ReceptorLengthLinkMER6MFR geneMFR proteinMGC17164MIP-1 Alpha-RMIP-1Alpha-RMIP1aRMYD-1MacrophageMacrophage Fusion ReceptorMacrophage Inflammatory Protein-1 Alpha ReceptorMalignantMalignant - descriptorMalignant Glial NeoplasmMalignant Glial TumorMalignant GliomaMalignant NeoplasmsMalignant Neuroglial NeoplasmMalignant Neuroglial TumorMalignant TumorMalignant Tumor of the BrainMalignant neoplasm of brainMediatingMiceMice MammalsModelingModern ManMolecular InteractionMonitorMonoclonal AntibodiesMultimodal TherapyMultimodal TreatmentMurineMusMφNK Cell ActivationNK CellsNatural Killer Cell ActivationNatural Killer CellsNormal TissueNormal tissue morphologyOncolyticOncolytic virusesOutcomeP84PD-1 antibodyPD-1/PD-L1PD-1/PDL1PD1 antibodyPD1-PD-L1PD1/PD-L1PD1/PDL1PK/PDPTPNS1PTPNS1 genePatientsProductionProtein-Tyrosine Phosphatase, Nonreceptor Type, Substrate 1Proteins Growth FactorsPublicationsPublishingRANTESRANTES Receptor GeneRANTES-RReceptor ProteinResearchSCYA5SHP Substrate 1SHPS1SIRP-Alpha-1SIRPASIS cytokinesSIS deltaSIS-deltaSISdSafetySamplingScheduleScientific PublicationSignal Regulatory Protein, Alpha Type, 1Signal TransductionSignal Transduction SystemsSignalingSmall Inducible Cytokine A5Solid NeoplasmSolid TumorSurfaceSurface Antigen Identified by Monoclonal Antibody 1D8SystemT cells for CART-Cell RANTES ProteinT-Cell Specific Protein p288T-CellsT-LymphocyteTCP228TGF-alpha ReceptorTestingTissuesToxic effectToxicitiesTransforming Growth Factor alpha ReceptorTumor CellTumor-infiltrating immune cellsTyrosine Phosphatase SHP Substrate 1Urogastrone ReceptorViralVirusVirus ReplicationaPD-1aPD1adoptive cell therapyadoptive cellular therapyanti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 monoclonal antibodiesanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyanti-tumor immune responseantiPD-1antibody dependent cell mediated cytotoxicityantibody dependent cytotoxicityantibody mediated cellular cytotoxicityantibody receptorantibody-dependent cell cytotoxicityantibody-dependent cellular cytotoxicityantibody-dependent cellular phagocytosisantibody-mediated cytotoxicityarmbio-markersbiologic markerbiological signal transductionbiomarkerc-erbB-1c-erbB-1 Proteincancer microenvironmentcancer progressioncancer virotherapycheck point blockadecheckpoint blockadechemoattractant cytokinechemokinechimeric antigen T cell receptorchimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cellschimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellscombination therapycombined modality treatmentcombined treatmentcytokinedesigndesigningdevelopmentalefficacy studyerbB-1erbB-1 Proto-Oncogene ProteinerbBlglioblastoma multiformeherpes simplex iherpes simplex virus 1 infectionherpes simplex virus infectionherpes simplex-1host responseimmune cell infiltrateimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check point blockadeimmune checkpoint blockadeimmune competentimmune modulationimmune regulationimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmuno therapyimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimprovedin vivoinfiltration of tumors by immune cellsinnovateinnovationinnovativeintratumoral immune cellintratumoral immune infiltratemAbsmalignancymanufacturemigrationmonoclonal Absmouse modelmulti-modal therapymulti-modal treatmentmurine modelneoplasm progressionneoplasm/cancerneoplastic cellneoplastic progressionnoveloncolysisoncolytic viral therapeuticoncolytic viral therapyoncolytic virotherapeuticoncolytic virotherapyoncolytic virus therapypatient prognosisperipheral bloodpharmacokinetics and pharmacodynamicspre-clinical efficacypre-clinical researchpre-clinical safetypre-clinical studypreclinical efficacypreclinical researchpreclinical safetypreclinical studypreventpreventingproto-oncogene protein c-erbB-1receptorrecruitresponsescaffoldscaffoldingspongioblastoma multiformesynergismtherapy optimizationthymus derived lymphocytetraffickingtreatment optimizationtumortumor immune celltumor immune infiltratetumor infiltration of immune cellstumor microenvironmenttumor progressionviral multiplicationviral replicationvirus multiplicationαPD-1αPD1
Description preview
PROJECT SUMMARY – PROJECT 4
The ultimate goal of this proposal is to develop a novel, effective, and safe oncolytic herpes simplex viral (oHSV)-
based immunotherapy for the treatment of glioblastoma (GBM), a highly fatal and the most common malignant
brain tumor. oHSV treatment of GBM relies on cancer-specific replication of the virus leading to…
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