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