2023
Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation
Bhagchandani S, Vohidov F, Milling L, Tong E, Brown C, Ramseier M, Liu B, Fessenden T, Nguyen H, Kiel G, Won L, Langer R, Spranger S, Shalek A, Irvine D, Johnson J. Engineering kinetics of TLR7/8 agonist release from bottlebrush prodrugs enables tumor-focused immune stimulation. Science Advances 2023, 9: eadg2239. PMID: 37075115, PMCID: PMC10115420, DOI: 10.1126/sciadv.adg2239.Peer-Reviewed Original ResearchConceptsToll-like receptor 7Cancer immunotherapyImmune stimulationMouse syngeneic tumor modelsNext-generation cancer immunotherapyImmune-related toxicitiesAcute systemic inflammationInnate immune cellsSyngeneic tumor modelsPotential cancer immunotherapySystemic inflammationImmune cellsReceptor 7Systemic administrationIntravenous administrationMyeloid cellsTumor growthSystemic toxicityTumor modelObservable systemic toxicityPotent stimulationImidazoquinolinesImmunotherapyStimulationProdrug
2021
766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs)
Bhagchandani S, Milling L, Liu B, Fessenden T, Spranger S, Johnson J, Irvine D. 766 Toward safe, systemic delivery of synthetic TLR7/8 agonists using Bottlebrush Prodrugs (BPDs). Journal For ImmunoTherapy Of Cancer 2021, 9: a801-a801. DOI: 10.1136/jitc-2021-sitc2021.766.Peer-Reviewed Original ResearchTLR reporter cellsSystemic deliveryAnti-PD-1 antibody treatmentMC38 colon cancer modelImidazoquinoline derivativesToll-like receptor agonistsSerum cytokine levelsMaximum tolerable doseSystemic side effectsImproved survival ratesReporter cellsAnti-tumor efficacyColon cancer modelCytokine levelsMetastatic diseaseTLR agonistsTLR7/8 agonistAntibody treatmentTLR activationTreatment of cancerTolerable doseReceptor agonistIntravenous administrationTopical solutionSide effects