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
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