Erythrocyte Encapsulated
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            -Asparaginase (Graspa) in Acute Leukemia

Thomas, Xavier; Jeune, Caroline Le

doi:10.2217/ijh-2016-0002

Cited by 29 publications

(15 citation statements)

References 115 publications

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“…In addition, allergic reactions, ranging from mild hypersensitivity reactions up to anaphylactic shock, can prevent the continuation of treatment [39,96]. To increase the half-life and reduce immunogenicity, therapeutic enzymes have been modified by conjugation to polyethylene glycol (PEG) [96], nanoparticle encapsulation [78], or erythrocyte encapsulation [97], and the treatment can be combined with immune-suppressive agents such as prednisone and dexamethasone. Furthermore, in silico and in vitro immunogenicity prediction tools can be used to assess the immunogenicity potential of a protein drug beforehand [98].…”

Section: Open Accessmentioning

confidence: 99%

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Butler

Meer

Leeuwen

2021

Trends in Endocrinology & Metabolism

170

124

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Targeting tumor cell metabolism is an attractive form of therapy, as it may enhance treatment response in therapy resistant cancers as well as mitigate treatment-related toxicities by reducing the need for genotoxic agents. To meet their increased demand for biomass accumulation and energy production and to maintain redox homeostasis, tumor cells undergo profound changes in their metabolism. In addition to the diversion of glucose metabolism, this is achieved by upregulation of amino acid metabolism. Interfering with amino acid availability can be selectively lethal to tumor cells and has proven to be a cancer specific Achilles' heel. Here we review the biology behind such cancer specific amino acid dependencies and discuss how these vulnerabilities can be exploited to improve cancer therapies.

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Section: Open Accessmentioning

confidence: 99%

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Butler

Meer

Leeuwen

2021

Trends in Endocrinology & Metabolism

170

124

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“…L-asparaginase, a bacterial-derived metabolic enzyme responsible for converting glutamine to glutamate, was previously identified to be promising in treating acute lymphoblastic leukemia (ALL). However, this was undermined by adverse side effects, such as immune–allergic responses and hepatotoxicities [ 163 , 164 ]. A recent technological advancement has allowed for L-asparaginase to be loaded onto red blood cells (ERY001), thereby improving its half-life and drastically reducing related toxicities and other adverse side-effects [ 165 ].…”

Section: Metabolic Interventions For Restricting Cancer Progressiomentioning

confidence: 99%

Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer

Lee

Yeo

et al. 2021

Cancers

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Cancer metabolism is a hallmark of cancer. Metabolic plasticity defines the ability of cancer cells to reprogram a plethora of metabolic pathways to meet unique energetic needs during the various steps of disease progression. Cell state transitions are phenotypic adaptations which confer distinct advantages that help cancer cells overcome progression hurdles, that include tumor initiation, expansive growth, resistance to therapy, metastasis, colonization, and relapse. It is increasingly appreciated that cancer cells need to appropriately reprogram their cellular metabolism in a timely manner to support the changes associated with new phenotypic cell states. We discuss metabolic alterations that may be adopted by cancer cells in relation to the maintenance of cancer stemness, activation of the epithelial–mesenchymal transition program for facilitating metastasis, and the acquisition of drug resistance. While such metabolic plasticity is harnessed by cancer cells for survival, their dependence and addiction towards certain metabolic pathways also present therapeutic opportunities that may be exploited.

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“…Formate dehydrogenase Methanol intoxication [264] Cyanide sulfurtransferase (rhodanase) Cyanide intoxication [65][66][67][68][69][70]265,266] Catalase, PEG-catalase Antioxidant [267] l-Asparaginase Antitumor therapy [16,22,24,[83][84][85][86]237,[268][269][270][271][272][273][274][275][276][277][278][279][280][281][282][283][284] l-Methioninase [87,88,285,286] Arginine deiminase [89,90] Hexokinase, glucose oxidase To decrease blood glucose (diabetes) [287,288] Insulin [138][139][140]289,290] Inositol hexaphosphate (IHP) Sickle...…”

Section: Active Substance Application Referencesmentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

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Erythrocyte Encapsulated L -Asparaginase (Graspa) in Acute Leukemia

Cited by 29 publications

References 115 publications

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer

Erythrocytes as Carriers: From Drug Delivery to Biosensors

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