2023
1069 IL-12 mRNA monotherapy is effective in murine tumors resistant to checkpoint inhibition
Santha S, Lakshmipathi J, Li M, Qian Y, Luheshi N, Politi K, Bosenberg M, Eyles J, Muthusamy V. 1069 IL-12 mRNA monotherapy is effective in murine tumors resistant to checkpoint inhibition. 2023, a1176-a1176. DOI: 10.1136/jitc-2023-sitc2023.1069.Peer-Reviewed Original ResearchCombinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance.
Krykbaeva I, Bridges K, Damsky W, Pizzurro G, Alexander A, McGeary M, Park K, Muthusamy V, Eyles J, Luheshi N, Turner N, Weiss S, Olino K, Kaech S, Kluger H, Miller-Jensen K, Bosenberg M. Combinatorial Immunotherapy with Agonistic CD40 Activates Dendritic Cells to Express IL12 and Overcomes PD-1 Resistance. Cancer Immunology Research 2023, 11: 1332-1350. PMID: 37478171, DOI: 10.1158/2326-6066.cir-22-0699.Peer-Reviewed Original ResearchConceptsPD-1 resistanceDendritic cellsTumor regressionAnti-PD-1 resistanceActivates Dendritic CellsCytokine secretion profilingSystemic cytokine profileTriple therapy combinationInnate immune activationAdaptive immune responsesComplete tumor regressionMajority of miceSignificant clinical challengeMouse melanoma modelT cell activationAgonistic CD40Checkpoint inhibitorsDC subsetsTriple therapyCytokine profileImmune activationCombinatorial immunotherapyTherapy combinationsT cellsClinical challengeTackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy
Wang Z, Muthusamy V, Petrylak D, Anderson K. Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy. Npj Precision Oncology 2023, 7: 70. PMID: 37479885, PMCID: PMC10362036, DOI: 10.1038/s41698-023-00417-5.Peer-Reviewed Original ResearchBladder cancerBC cellsEarly phase clinical trialsPhase clinical trialsDurable responsesMetastatic diseaseMost patientsFGFR3 alterationsPrevalent malignancyClinical trialsFGFR3 fusionsPreclinical studiesFGFR inhibitorsHDAC inhibitorsFGFR3 expressionEfficient therapyTherapyCancerQuisinostatFGFR3New mechanistic insightsInhibitorsCellsPatientsMalignancy
2022
Comprehensive Analysis of Metabolic Isozyme Targets in Cancer
Marczyk M, Gunasekharan V, Casadevall D, Qing T, Foldi J, Sehgal R, Shan NL, Blenman KRM, O'Meara TA, Umlauf S, Surovtseva YV, Muthusamy V, Rinehart J, Perry RJ, Kibbey R, Hatzis C, Pusztai L. Comprehensive Analysis of Metabolic Isozyme Targets in Cancer. Cancer Research 2022, 82: 1698-1711. PMID: 35247885, PMCID: PMC10883296, DOI: 10.1158/0008-5472.can-21-3983.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetAcetyl-CoA carboxylase 1Therapeutic targetCancer typesCell linesBreast cancer viabilityPatient-derived xenograftsNovel metabolic targetsCorresponding cell linesExpression patternsDrug treatmentMatching normal tissuesRelated commentaryTumor growthMalignant transformationSmall molecule inhibitionCancer viabilityCancer Cell Line EncyclopediaNormal tissuesMetabolic vulnerabilitiesCarboxylase 1Anticancer therapyCellular changesCell proliferationMetabolic reprogramming
2021
Bifunctional small molecules that mediate the degradation of extracellular proteins
Caianiello DF, Zhang M, Ray JD, Howell RA, Swartzel JC, Branham EMJ, Chirkin E, Sabbasani VR, Gong AZ, McDonald DM, Muthusamy V, Spiegel DA. Bifunctional small molecules that mediate the degradation of extracellular proteins. Nature Chemical Biology 2021, 17: 947-953. PMID: 34413525, DOI: 10.1038/s41589-021-00851-1.Peer-Reviewed Original ResearchConceptsExtracellular proteinsTarget proteinsUbiquitin-proteasome systemBifunctional small moleculesSynthetic moleculesProtein degradationIntracellular proteinsProinflammatory cytokine proteinProteinLysosomal proteasesTernary complexSmall moleculesPromising therapeutic strategyCytokine proteinsTherapeutic strategiesMoleculesDegradationProteaseDisease treatmentExperimental evidence
2019
Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses
Jiang X, Muthusamy V, Fedorova O, Kong Y, Kim DJ, Bosenberg M, Pyle AM, Iwasaki A. Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses. Journal Of Experimental Medicine 2019, 216: 2854-2868. PMID: 31601678, PMCID: PMC6888973, DOI: 10.1084/jem.20190801.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Agents, ImmunologicalCD8-Positive T-LymphocytesDose-Response Relationship, DrugGene Expression ProfilingImmunologic MemoryInjections, IntralesionalMaleMelanoma, ExperimentalMiceOligoribonucleotidesProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceTumor BurdenConceptsAntitumor responseNucleic acid-sensing pathwaysSignificant tumor growth delayNumber of CD8Systemic antitumor responseRobust antitumor responseAnti-PD1 antibodyB16 tumor growthImmunogenic tumor modelsCytosolic nucleic acid-sensing pathwaysSingle-agent treatmentTumor growth delayTumor metastasis modelNK cellsMetastasis modelT lymphocytesImmune responseExtended survivalIntratumoral deliveryImmune memoryMyeloid cellsTumor growthGrowth delayTumor microenvironmentTumor model
2017
Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics
Chirkin E, Muthusamy V, Mann P, Roemer T, Nantermet PG, Spiegel DA. Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics. Angewandte Chemie International Edition 2017, 56: 13036-13040. PMID: 28793176, DOI: 10.1002/anie.201707536.Peer-Reviewed Original ResearchConceptsImportant public health concernNovel therapeutic approachesHuman immune cellsSystemic fungal infectionsPublic health concernAntibody-recruiting moleculesFungal illnessImmune cellsNew antifungal agentsTreatment strategiesTherapeutic approachesEndogenous antibodiesRelevant functional assaysFungal infectionsHealth concernFunctional assaysAntifungal agentsNon-peptidic small moleculesC. albicans cellsCandida albicansCellsBiological evaluationAlbicans cellsImmunotherapeuticsIllnessNeutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics
Chirkin E, Muthusamy V, Mann P, Roemer T, Nantermet P, Spiegel D. Neutralization of Pathogenic Fungi with Small‐Molecule Immunotherapeutics. Angewandte Chemie 2017, 129: 13216-13220. DOI: 10.1002/ange.201707536.Peer-Reviewed Original ResearchImportant public health concernNovel therapeutic approachesHuman immune cellsSystemic fungal infectionsPublic health concernAntibody-recruiting moleculesFungal illnessImmune cellsNew antifungal agentsTreatment strategiesTherapeutic approachesEndogenous antibodiesRelevant functional assaysFungal infectionsHealth concernFunctional assaysAntifungal agentsNon-peptidic small moleculesC. albicans cellsCandida albicansCellsBiological evaluationAlbicans cellsImmunotherapeuticsIllness(S029) Development of an Immune-Associated Molecular Signature Predicting Melanoma Survival
Micevic G, Muthusamy V, Pupo G, Scolyer R, Long G, Bosenberg M. (S029) Development of an Immune-Associated Molecular Signature Predicting Melanoma Survival. International Journal Of Radiation Oncology • Biology • Physics 2017, 98: e9. DOI: 10.1016/j.ijrobp.2017.02.065.Peer-Reviewed Original Research
2016
Re‐engineering the Immune Response to Metastatic Cancer: Antibody‐Recruiting Small Molecules Targeting the Urokinase Receptor
Rullo A, Fitzgerald K, Muthusamy V, Liu M, Yuan C, Huang M, Kim M, Cho A, Spiegel D. Re‐engineering the Immune Response to Metastatic Cancer: Antibody‐Recruiting Small Molecules Targeting the Urokinase Receptor. Angewandte Chemie 2016, 128: 3706-3710. DOI: 10.1002/ange.201510866.Peer-Reviewed Original ResearchAntibody-recruiting small moleculeUrokinase-type plasminogen activator receptorMetastatic cancerPlasminogen activator receptorAntibody-recruiting moleculesCancer cell surface markersCell surface markersImmune responseNon-peptide ligandsTumor growthActivator receptorWeight lossCancer cellsCancerAgent doxorubicinUrokinase receptorReceptorsImmunotherapeuticsSmall moleculesSelective strategy