grant
Optimization of an active mutant KRAS peptide vaccine in colorectal cancer
Organization JOHNS HOPKINS UNIVERSITYLocation BALTIMORE, UNITED STATESPosted 10 Jan 2025Deadline 31 Dec 2029
NIHUS FederalResearch GrantFY2025AntibodiesAntigen PresentationAntigenic DeterminantsAntitumor ResponseArchitectureAutoantigensAutologous AntigensBinding DeterminantsBiological Response ModifiersBiomodulatorsBloodBlood Reticuloendothelial SystemC-K-RASCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCT-26CT26Cancer CauseCancer EtiologyCancer ModelCancerModelCell BodyCell Communication and SignalingCell SignalingCellsCessation of lifeCheckpoint inhibitorClass I GenesClinicalClinical TrialsColorectal CancerCombined Modality TherapyCytometryDNA mutationDataDeathDigestive Tract TumorDigestive TumorDiseaseDisorderDown-RegulationEngineeringEngineering / ArchitectureEnrollmentEpitopesEvaluableEvaluable DiseaseGI NeoplasmGI Tract TumorGI TumorGastrointestinal NeoplasmsGastrointestinal Tract TumorGastrointestinal TumorGenetic ChangeGenetic defectGenetic mutationHepatic Neoplasm SecondaryHepatic metastasisHumanImageImmuneImmune EvasionImmune MediatorsImmune Mediators/ModulatorsImmune checkpoint inhibitorImmune mediated therapyImmune responseImmunesImmunochemical ImmunologicImmunologicImmunologicalImmunologicallyImmunologically Directed TherapyImmunologicsImmunomodulationImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyImpairmentIn VitroIntracellular Communication and SignalingK-RAS2AK-RAS2BK-RasK-Ras 2AK-Ras-2 OncogeneKRASKRAS driven oncogenesisKRAS oncogenesisKRAS(G12D)KRAS-driven tumorigenesisKRAS-mediated tumorigenesisKRAS2KRAS2 geneKRASG12DKi-RASLeadLettersLiver secondariesLiver secondary cancerMEKsMHC Class IMHC Class I GenesMaintenanceMemoryMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to the LiverMetastatic TumorMetastatic Tumor to the LiverMetastatic malignant neoplasm to liverMiceMice MammalsMicrosatellite MarkersMicrosatellite RepeatsMicrosatellitesModalityModelingModern ManMultimodal TherapyMultimodal TreatmentMurineMusMutationNeoplasm MetastasisNeoplasm of the Digestive TractNeoplasm of the GI TractNeoplasm of the Gastrointestinal TractNivolumabOncogene K-RasOncogenesisOpdivoOrganoidsOutcomePD-1 antibodyPD1 antibodyPancreas Ductal AdenocarcinomaPancreatic Ductal AdenocarcinomaPatientsPb elementPeptide VaccinesPeptidesPeripheralPhase 2 Clinical TrialsPhase II Clinical TrialsPhenotypePilot ProjectsProductionRASK2RecurrenceRecurrentRefractoryRegimenReportingResectedSafetySecondary NeoplasmSecondary TumorSelf-AntigensSignal TransductionSignal Transduction SystemsSignalingSomatic MutationSurvival RateT cell receptor repertoire sequencingT cell receptor sequencingT cell responseT-Cell ActivationT-CellsT-LymphocyteT-cell receptor repertoireT8 CellsT8 LymphocytesTCR repertoireTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTestingTherapeuticTranslationsTreatment EfficacyTumor CellTumor EscapeTumor Immune EscapeTumor ImmunityTumor TissueUnited StatesUpregulationVaccine AntigenVaccineeVaccinesYervoyaCTLA-4aCTLA-4 antibodiesaCTLA4aPD-1aPD1activate T cellsanti programmed cell death 1anti-CTLA-4anti-CTLA-4 antibodiesanti-CTLA4anti-CTLA4 antibodiesanti-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 immunityanti-tumor responseantiPD-1antitumor immunitybiological signal transductioncancer evasioncancer immune escapecancer immune evasioncancer immunitycancer metastasiscancer microenvironmentcentral tolerancecheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapychemotherapycohortcolon cancer cell linecolon cancer patientscolorectal cancer cell linecolorectal cancer patientscombination therapycombined modality treatmentcombined treatmentcytokinedetermine efficacydevelop a vaccinedevelop vaccinesdevelopment of a vaccinedigestive neoplasmefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationefficacy testingengineered T cellsenrollevaluate efficacyexamine efficacyexhaustiongenetically engineered T-cellsgenome mutationheavy metal Pbheavy metal leadhost responseimagingimmune check point inhibitorimmune check point therapyimmune checkpoint therapyimmune evasiveimmune modulationimmune regulationimmune resistanceimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmune-resistantimmuno therapyimmunogenicityimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimmunoresistanceimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimprovedin vivoinhibitorintervention efficacyipilimumabliver metastasesmalignant liver neoplasm, specified as secondarymetastasis in the livermetastasis to the livermetastasize to the livermetastatic cancer to livermetastatic colo-rectalmetastatic colo-rectal cancermetastatic colo-rectal carcinomametastatic colon cancermetastatic colorectalmetastatic colorectal cancermetastatic colorectal carcinomametastatic livermetastatic liver neoplasmmortalitymouse modelmulti-modal therapymulti-modal treatmentmurine modelmutantneo-antigenneo-epitopesneoantigensneoepitopesneoplastic cellnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapyoncogene addictiononcogenic KRASparticipant enrollmentpatient enrollmentpatient responsepatient specific responsepermissivenessphase II protocolpilot studyprogramsrecruitresponseresponsive patientscRNA sequencingscRNA-seqsecondary liver malignancysecondary malignant liver neoplasmselective expressionselectively expressedsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsmall molecular inhibitorsmall molecule inhibitorsomatic varianttheoriestherapeutic efficacytherapy efficacythymus derived lymphocytetransgenic T- cellstranslationtreatment strategytumortumor cell metastasistumor evasiontumor immune evasiontumor microenvironmenttumorigenesisv-Ki-RAS2 Kirsten Rat Sarcoma 2 Viral Oncogene Homologvaccinated individualvaccinated participantvaccinated patientvaccinated personvaccinated subjectvaccine developmentvaccine for immunotherapyvaccine immunotherapyvaccine-based immunotherapyα-CTLA-4α-CTLA4αCTLA-4αCTLA4αPD-1αPD1
Description preview
PROJECT SUMMARY.
Colorectal cancer (CRC) is the second leading cause of cancer–related mortality in the U.S. with a dismal 5–
year overall survival rate at <15% for those with metastases. Immune checkpoint inhibitors (ICIs) lack therapeutic
efficacy in the majority (~95%) of advanced CRC tumors that are microsatellite stable (MSS). Mutations in…
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