2021
Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity
Gayle S, Aiello R, Leelatian N, Beckta JM, Bechtold J, Bourassa P, Csengery J, Maguire RJ, Marshall D, Sundaram RK, Van Doorn J, Jones K, Moore H, Lopresti-Morrow L, Paradis T, Tylaska L, Zhang Q, Visca H, Reshetnyak YK, Andreev OA, Engelman DM, Glazer PM, Bindra RS, Paralkar VM. Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity. NAR Cancer 2021, 3: zcab021. PMID: 34316708, PMCID: PMC8210154, DOI: 10.1093/narcan/zcab021.Peer-Reviewed Original ResearchAntigen-independent mannerTherapeutic indexTumor growthSystemic toxicityHigh unmet needFavorable therapeutic indexHuman tumor modelsTopoisomerase inhibitorsSevere systemic toxicityHigh therapeutic indexRibose polymerase inhibitorsHuman solid tumorsSuppress tumor growthTumor cell killingAntibody-drug conjugatesSynergistic tumor cell killingUniversal tumorSpecific antigenSolid tumorsUnmet needPARP inhibitorsTumor modelCytotoxic payloadDNA repair inhibitorsPolymerase inhibitors
2020
Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation
Kaplan AR, Pham H, Liu Y, Oyaghire S, Bahal R, Engelman DM, Glazer PM. Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation. Molecular Cancer Research 2020, 18: 873-882. PMID: 32098827, PMCID: PMC7272299, DOI: 10.1158/1541-7786.mcr-19-0661.Peer-Reviewed Original ResearchConceptsCancer cellsTumor cellsLocal tumor irradiationTumor-selective radiosensitizationMouse tumor modelsKu80 expressionNovel agentsTumor irradiationTumor growthTumor microenvironmentTumor modelRadiation treatmentTherapeutic agentsSubcutaneous mouse tumor modelTumorsMiceCancer therapyHealthy tissueAcute toxicitySpecific targetingSelective effectPNA antisenseTumor-SelectiveAcidic culture conditionsSensitize cancer cells