The mouse immune response to carrier erythrocyte entrapped antigens

Murray, Anne M.; Pearson, Ian F.S.; Fairbanks, Lynette D.; Chalmers, R. A.; Bain, Murray D.; Bax, Bridget E.

doi:10.1016/j.vaccine.2006.05.013

Cited by 31 publications

(24 citation statements)

References 47 publications

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“…In addition to optimized delivery of antigens, carrier RBC plays a role of the adjuvant, by presenting multiple copies of antigens and stimulating non-specific immune response96. Further, encapsulation of cytokines including interleukins and interferon into RBC facilitates delivery of these agents to macrophages97, resulting in stimulation of immune response in animal models98.…”

Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcmentioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

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Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

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Section: Vascular Delivery Of Drugs Encapsulated Into Carrier Rbcmentioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

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“…The work reported here does not allow definition of the particular role of blood cellular elements in the generation of TI and TD xenoantibodies. However, previous data suggest that erythrocytes may be mainly involved in the production of TI and leukocytes in TD xenoantibodies [21,22]. …”

Section: Discussionmentioning

confidence: 99%

Boosted Rat Natural Xenoantibodies Cross-React with <b><i>Enterococcus faecalis</i></b> by Targeting Melibiose and <smlcap>L</smlcap>-Rhamnose

2013

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Natural antibodies include a subset described as xenoantibodies considered to be directed at microorganisms and also cross-react with antigens of unrelated species. In this study, we generated T-cell-independent (TI) and T-cell-dependent (TD) xenoantibodies in Lewis rats with hamster and pig blood injections. TI anti-hamster and anti-pig IgM and IgG xenoantibodies cross-reacted with Enterococcus faecalis but not with Escherichia coli isolated from the blood of Lewis rats after cecal ligation and puncture (CLP). TI anti-pig IgM xenoantibodies also showed some reactivity with two human blood isolates of E. faecalis. In contrast, TD xenoantibodies did not show any reactivity with rat or human bacteria. TI and TD anti-hamster and anti-pig IgM and IgG xenoantibodies showed cross-reactivity with lymphocytes and endothelial cells from species distinct to that used for immunization. Glycan array analysis and inhibition assays identified antibodies against melibiose and L-rhamnose as mediators of anti-hamster and anti-porcine xenoantibody cross-reactivity with E. faecalis. A rise in TI anti-hamster and anti-pig xenoantibodies was accompanied by decreased survival of Lewis rats in a low-severity sepsis model of CLP. Therefore, TI xenoantibodies in the rat include anti-carbohydrate antibodies reactive to bacteria of endogenous flora. Enhancement of these antibodies may result in more severe infectious diseases caused by these microorganisms.

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“…RBC-mediated delivery may induce tolerance through the induction of regulatory T cells[124]. Reduced immunogenicity of therapeutic enzymes by encapsulation within RBCs[49, 125] has also been attributed to separation of the cargo from immune system by the RBC plasma membrane. Nevertheless, the consequences of exposing RBC components normally hidden from the immune system caused by loading and potential immunogenicity of a fraction of the drug cargo retained on the RBC surface must be carefully examined for each intended use.…”

Section: Effects Of Drugs On Rbcsmentioning

confidence: 99%

Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond

Villa

Cines

Siegel

et al. 2017

Transfusion Medicine Reviews

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Red blood cells (RBCs) are innate carriers that can also be engineered to improve the pharmacokinetics and pharmacodynamics of many drugs, particularly bio-therapeutics. Successful loading of drugs, both internally and on the external surface of RBCs, has been demonstrated for many drugs including anti-inflammatory, anti-microbial, and anti-thrombotic agents. Methods for internal loading of drugs within RBCs are now entering clinical use. While internal loading can result in membrane disruption that may compromise biocompatibility, surface loading using either affinity or chemical ligands offers a diverse set of approaches for the production of RBC drug carriers. A wide range of surface determinants is potentially available for this approach, although there remains a need to characterize the effects of coupling agents to these surface proteins. Somewhat surprisingly, recent data also suggest that red cell mediated delivery may confer tolerogenic immune effects. Questions remaining before widespread application of these technologies include determining the optimal loading protocol, source of RBCs, and production logistics, as well as addressing regulatory hurdles. RBC drug carriers, after many decades of progress, are now poised to enter the clinic and broaden the potential application of RBCs in blood transfusion.

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The mouse immune response to carrier erythrocyte entrapped antigens

Cited by 31 publications

References 47 publications

Drug delivery by red blood cells: vascular carriers designed by mother nature

Drug delivery by red blood cells: vascular carriers designed by mother nature

Boosted Rat Natural Xenoantibodies Cross-React with <b><i>Enterococcus faecalis</i></b> by Targeting Melibiose and <smlcap>L</smlcap>-Rhamnose

Erythrocytes as Carriers for Drug Delivery in Blood Transfusion and Beyond

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