Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study

Faivre, Sandrine; Mir, Olivier; Dreyer, Chantal; Ropert, Stanislas; Bouattour, Mohamed; Desjardins, Robert E.; Goldwasser, François; Raymond, Éric

doi:10.2147/ijn.s110274

Cited by 23 publications

(6 citation statements)

References 27 publications

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“…The SN38 drug cannot be administered directly due to its high insolubility, then the DTS-108, a water-soluble compound comprising SN38 linked to the highly charged oligopeptide DPV1047 (Vectocell1), has been produced and evaluated in preclinical and clinical studies [ 183 , 184 ]. The antitumoral efficacy of DTS-108 was dose-dependent when evaluated in lung human tumors and superior to irinotecan [ 185 ], while DTS-108, a novel peptidic pro-drug of SN38, has been used in a phase I clinical study for the treatment of advanced/metastatic solid tumors [ 186 ].…”

Section: Discussionmentioning

confidence: 99%

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents

et al. 2018

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Cell membranes with their selective permeability play important functions in the tight control of molecular exchanges between the cytosol and the extracellular environment as the intracellular membranes do within the internal compartments. For this reason the plasma membranes often represent a challenging obstacle to the intracellular delivery of many anti-cancer molecules. The active transport of drugs through such barrier often requires specific carriers able to cross the lipid bilayer. Cell penetrating peptides (CPPs) are generally 5–30 amino acids long which, for their ability to cross cell membranes, are widely used to deliver proteins, plasmid DNA, RNA, oligonucleotides, liposomes and anti-cancer drugs inside the cells. In this review, we describe the several types of CPPs, the chemical modifications to improve their cellular uptake, the different mechanisms to cross cell membranes and their biological properties upon conjugation with specific molecules. Special emphasis has been given to those with promising application in cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents

et al. 2018

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“…Few clinical trials using CPPs have been published to date, mostly in the context of cancer diagnosis and therapeutics [159][160][161]. Twenty-seven patients with breast cancer received intra-operative activatable fluorescent peptide to improve tumor margin detection and assist with complete tumor resection [162].…”

Section: Hurdles To Clinical Applicationmentioning

confidence: 99%

Cell Penetrating Peptides, Novel Vectors for Gene Therapy

2020

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Cell penetrating peptides (CPPs), also known as protein transduction domains (PTDs), first identified ~25 years ago, are small, 6–30 amino acid long, synthetic, or naturally occurring peptides, able to carry variety of cargoes across the cellular membranes in an intact, functional form. Since their initial description and characterization, the field of cell penetrating peptides as vectors has exploded. The cargoes they can deliver range from other small peptides, full-length proteins, nucleic acids including RNA and DNA, liposomes, nanoparticles, and viral particles as well as radioisotopes and other fluorescent probes for imaging purposes. In this review, we will focus briefly on their history, classification system, and mechanism of transduction followed by a summary of the existing literature on use of CPPs as gene delivery vectors either in the form of modified viruses, plasmid DNA, small interfering RNA, oligonucleotides, full-length genes, DNA origami or peptide nucleic acids.

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“…There is also an example of a staple peptide in ALRN-6924 [ 136 ]. In spite of the drawbacks of native sequences, some examined candidates contained this form of peptide, such as DPV1047 in DTS-108 [ 236 ], Tat in KAI-9803 [ 237 ], Arg11 in ATX-101 [ 238 ], DPTsh-1 in Pep-010 [ 239 ], Angiopep-2 in ANG1005 [ 240 ], which were also used in clinical trials.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System

et al. 2022

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Cell-penetrating peptides (CPP) are promising tools for the transport of a broad range of compounds into cells. Since the discovery of the first members of this peptide family, many other peptides have been identified; nowadays, dozens of these peptides are known. These peptides sometimes have very different chemical–physical properties, but they have similar drawbacks; e.g., non-specific internalization, fast elimination from the body, intracellular/vesicular entrapment. Although our knowledge regarding the mechanism and structure–activity relationship of internalization is growing, the prediction and design of the cell-penetrating properties are challenging. In this review, we focus on the different modifications of well-known CPPs to avoid their drawbacks, as well as how these modifications may increase their internalization and/or change the mechanism of penetration.

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Pharmacokinetics and safety of DTS-108, a human oligopeptide bound to SN-38 with an esterase-sensitive cross-linker in patients with advanced malignancies: a Phase I study

Cited by 23 publications

References 27 publications

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents

Cell Penetrating Peptides as Molecular Carriers for Anti-Cancer Agents

Cell Penetrating Peptides, Novel Vectors for Gene Therapy

Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System

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