Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems

Rothdiener, Miriam; Müller, Dafne; Castro, Patricia Garrido; Scholz, Anja; Schwemmlein, Michael; Fey, Georg H.; Heidenreich, Olaf; Kontermann, Roland E.

doi:10.1016/j.jconrel.2010.02.020

Cited by 50 publications

(31 citation statements)

References 46 publications

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“…So far an immunotoxin (Du et al, 2007), a fusion of IL-3 with a truncated version of diphtheria toxin (Feuring-Buske et al, 2002;Frankel et al, 2008), a neutralizing full-length antibody (7G3; Jin et al, 2009), and a bispecific single-chain Fv (bsscFv; Stein et al, 2010) directed against CD123 have been described, and the monoclonal antibody (mAb) 7G3 has been tested in a phase I clinical study (Roberts et al, 2008; http://clinicaltrials.gov/ ct2/show/NCT00401739?term=CSL360&rank=1). Well-studied antibody-derived agents directed against CD33 include, apart from GO an immunotoxin (Schwemmlein et al, 2006), a fusion protein between a single chain Fv antibody fragment (scFv) and the sTRAIL death receptor ligand (ten Cate et al, 2009), and siRNA-loaded liposomes coated with CD33-directed scFvs (Rothdiener et al, 2010).…”

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confidence: 99%

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

et al. 2010

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Two trivalent constructs consisting of single-chain Fv antibody fragments (scFvs) specific for the interleukin-3 receptor a chain (CD123), CD33 and the Fcc-receptor III (CD16) were designed and characterized for the elimination of acute myeloid leukaemia (AML) cells. The dual targeting single-chain Fv triplebody (sctb) [123 · ds16 · 33] and the mono targeting sctb [123 · ds16 · 123] both specifically bound their respective target antigens and were stable in human serum at 37°C for at least 5 d. Both constructs induced potent antibody-dependent cellular cytotoxicity (ADCC) of two different AML-derived CD33-and CD123 double-positive cell lines in the low picomolar range using isolated mononuclear cells (MNCs) as effector cells. In these experiments the dual targeting molecule produced significantly stronger lysis than the mono targeting agent. In addition, the sctbs showed a high potency in mediating ADCC of primary leukaemia cells isolated from peripheral blood or bone marrow of seven AML patients. Hence, these novel molecules displayed potent anti-leukaemic effects against AML cells in vitro and represent attractive candidates for further preclinical development.

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confidence: 99%

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

et al. 2010

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“…To create this construct, the scFv subunits were disulfide-stabilized 78-80 humanized 81-83 and stability-engineered 84 by standard procedures. The TransIT®-LT1 transfection reagent (Mirus Bio LLC, catalog # MIR 2300) was used for transfection according to the manufacturer´s protocol to generate a stable cell pool of Freestyle TM 293F cells (ThermoFisher Scientific, cat.…”

Section: Methodsmentioning

confidence: 99%

Dual-targeting triplebody 33-16-123 (SPM-2) mediates effective redirected lysis of primary blasts from patients with a broad range of AML subtypes in combination with natural killer cells

et al. 2018

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A number of agents designed for immunotherapy of Acute Myeloid Leukemia (AML) are in preclinical and early clinical development. Most of them target a single antigen on the surface of AML cells. Here we describe the development and key biological properties of a tri-specific agent, the dual-targeting triplebody SPM-2, with binding sites for target antigens CD33 and CD123, and for CD16 to engage NK cells as cytolytic effectors. Primary blasts of nearly all AML patients carry at least one of these target antigens and the pair is particularly promising for the elimination of blasts and leukemia stem cells (LSCs) from a majority of AML patients by dual-targeting agents. The cytolytic activity of NK cells mediated by SPM-2 was analyzed in vitro for primary leukemic cells from 29 patients with a broad range of AML-subtypes. Blasts from all 29 patients, including patients with genomic alterations associated with an unfavorable genetic subtype, were lysed at nanomolar concentrations of SPM-2. Maximum susceptibility was observed for cells with a combined density of CD33 and CD123 above 10,000 copies/cell. Cell populations enriched for AML-LSCs (CD34pos and CD34pos CD38neg cells) from 2 AML patients carried an increased combined antigen density and were lysed at correspondingly lower concentrations of SPM-2 than unsorted blasts. These initial findings raise the expectation that SPM-2 may also be capable of eliminating AML-LSCs and thus of prolonging survival. In the future, patients with a broad range of AML subtypes may benefit from treatment with SPM-2.

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“…50,72 First, ligands such as maleimide and succinyl were coupled to the active end group of PEG-DSPE. Secondly, the ligand-PEG-DSPE was transferred into the outer monolayer of preformed, drug-loaded liposomes by simple incubation 50,73 ( Figure 3C). During the postinsertion method, a variety of ligand-PEG-DSPE copolymers were inserted into various preformed liposomes containing different drugs, allowing ligandtargeted therapeutics in individual patients.…”

Section: Postinsertion Methodsmentioning

confidence: 99%

“…[49][50][51] MAbs contains fragments (Fab), complementarity-determining regions and fragmentcrystallizable region (Fc), but fragments do not include Fc. Their targeting are somewhat different.…”

Section: Antibody Targeting Moietiesmentioning

confidence: 99%

Application of poly(ethylene glycol)– distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery

Wang

Xiao²,

Zeng³

et al. 2012

IJN

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Poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers are biocompatible and amphiphilic polymers that can be widely utilized in the preparation of liposomes, polymeric nanoparticles, polymer hybrid nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, and microemulsions. Particularly, the terminal groups of PEG can be activated and linked to various targeting ligands, which can prolong the circulation time, improve the drug bioavailability, reduce undesirable side effects, and especially target specific cells, tissues, and even the intracellular localization in organelles. This review herein aims to describe recent developments in drug carriers exploiting PEG-DSPE block copolymers and their derivatives, and the incorporation of different ligands to the end groups of PEG-DSPE to target delivery, focusing on their modification approaches, advantages, applications, and the probable associated drawbacks.

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Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems

Cited by 50 publications

References 46 publications

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

Dual-targeting triplebody 33-16-123 (SPM-2) mediates effective redirected lysis of primary blasts from patients with a broad range of AML subtypes in combination with natural killer cells

Application of poly(ethylene glycol)– distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery

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Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems

Cited by 50 publications

References 46 publications

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

A recombinant trispecific single‐chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting

Dual-targeting triplebody 33-16-123 (SPM-2) mediates effective redirected lysis of primary blasts from patients with a broad range of AML subtypes in combination with natural killer cells

Application of poly(ethylene glycol)&ndash; distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery

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Application of poly(ethylene glycol)– distearoylphosphatidylethanolamine (PEG-DSPE) block copolymers and their derivatives as nanomaterials in drug delivery