The effect of CD47 modified polymer surfaces on inflammatory cell attachment and activation

Stachelek, Stanley J.; Finley, Matthew J.; Alferiev, Ivan S.; Wang, Fengxiang; Tsai, Richard K.; Eckells, Edward C.; Tomczyk, Nancy; Connolly, Jeanne M.; Discher, Dennis E.; Eckmann, David M.; Levy, Robert J.

doi:10.1016/j.biomaterials.2011.02.053

Cited by 73 publications

(103 citation statements)

References 35 publications

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“…CD47-SIRPα signalling in murine immunoglobulin-opsonised red blood cells (RBC) as well as in human CD47 + -RBC and CD47 + -microparticles leads to inhibition of ingestion by macrophages(1,6). CD47- activated polyvinyl chloride (PVC) and polyurethane (PU) surfaces demonstrated reduced cell adherence and neutrophil activation when compared to non-activated polymers(7) and coating of nanoparticles with CD47 + -RBC-membranes minimized particle up-take by macrophages(8). Therefore, use of CD47 has been proposed for the development of “stealth” particles for drug delivery(9–12).…”

Section: Introductionmentioning

confidence: 99%

CD47 EnhancesIn VivoFunctionality of Artificial Antigen-Presenting Cells

Bruns

Bessell

Varela

et al. 2015

Clinical Cancer Research

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Purpose Artificial Antigen-Presenting Cells, aAPC, have successfully been used to stimulate antigen-specific T cell responses in vitro as well as in vivo. While aAPC compare favorable to autologous dendritic cells in vitro, their effect in vivo might be diminished through rapid clearance by macrophages. Therefore, to prevent uptake and minimize clearance of aAPC by macrophages, and thereby increasing in vivo functionality, we investigated the efficiency of “don’t eat me” three-signal aAPC compared to classical two-signal aAPC. Experimental Design To generate “don’t eat me” aAPC, CD47 was additionally immobilized onto classical aAPC (aAPCCD47+). aAPC and aAPCCD47+ were analyzed in in vitro human primary T cell and macrophage co-cultures. In vivo efficiency was compared in a NOD/SCID T cell proliferation and a B16-SIY melanoma model. Results This study demonstrates that aAPCCD47+ in co-culture with human macrophages show a CD47 concentration dependent inhibition of phagocytosis, while their ability to generate and expand antigen-specific T cells was not affected. Furthermore, aAPCCD47+ generated T cells displayed equivalent killing abilities and polyfunctionality when compared to aAPC generated T cells. In addition, in vivo studies demonstrated an enhanced stimulatory capacity and tumor inhibition of aAPCCD47+ over normal aAPC in conjunction with diverging bio-distribution in different organs. Conclusion Our data for the first time show that aAPC functionalized with CD47 maintain their stimulatory capacity in vitro and demonstrate enhanced in vivo efficiency. Thus this next generation aAPCCD47+ have a unique potential to enhance the application of the aAPC technology for future immunotherapy approaches.

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Section: Introductionmentioning

confidence: 99%

CD47 EnhancesIn VivoFunctionality of Artificial Antigen-Presenting Cells

Bruns

Bessell

Varela

et al. 2015

Clinical Cancer Research

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“…Other strategies, to name a few, to prolong circulation are surface coating of carrier with zwitterionic compounds [117] or coupling of CD47 proteins to the carrier surface. CD47 interacts with SIRPα present on leukocytes, which impedes phagocytosis [120]. Yet, coupling of CD47 on the surface of carriers can result in reduction of surface density of targeting moiety.…”

Section: Surface Properties Of Carriersmentioning

confidence: 99%

Receptor-targeted Drug delivery: Current Perspective and Challenges

et al. 2014

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Receptor-targeted drug delivery has been extensively explored for active targeting. However, the scarce clinical applications of such delivery systems highlight the implicit hurdles in development of such systems. These hurdles begin with lack of knowledge of differential expression of receptors, their accessibility and identification of newer receptors. Similarly, ligand-specific challenges range from proper choice of ligand and conjugation chemistry, to release of drug/delivery system from ligand. Finally, nanocarrier systems, which offer improved loading, biocompatibility and reduced premature degradation, also face multiple challenges. This review focuses on understanding these challenges, and means to overcome such challenges to develop efficient, targeted drug-delivery systems.

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“…CD47 binding to SIRP inhibits phagocytosis, in part via regulation of the cytoskeleton and inhibition of engulfing structures. Incorporation of CD47 on drug carrier surfaces reduces attachment to neutrophils and macrophages, therefore prolonging circulation and inhibiting inflammation (Stachelek, et al, 2011). In addition to controlling the solubility level, half-life in circulation, and immune system recognition, nanocarriers can also improve control of the drug efficacy upon release in the case of therapeutic interventions where administration is local.…”

Section: Circulation and Clearancementioning

confidence: 99%