2023
Combinatorial 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 challenge
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
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 cellsImmunotherapeuticsIllness