Monoclonal anti‐A antibody removal by synthetic A antigen immobilized on specific antibody filters

Gautam, Shalini; Korchagina, Elena; Bovin, Nicolai V.; Federspiel, William J.

doi:10.1002/bit.21621

Cited by 4 publications

(20 citation statements)

References 43 publications

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“…2,13,18,19 An ideal antibody filtering device selectively removes up to 100% of the target antibodies in a 2-4 h time period and is biocompatible and simple to operate. To meet these design goals, we developed a new antibody filtration device containing microfiltration fibers with antibody capturing beads integrated within the interstitial fiber space (BSAF device).…”

Section: Discussionmentioning

confidence: 99%

“…In each case, k L was calculated from fitting the reservoir antibody concentrations at various times to Eq. (13). The results of the fits of Eq.…”

Section: Measurement Of Model Parameters and Adsorption Capacity Of Mmentioning

confidence: 97%

“…Whole blood perfuses through the fibers and the targeted antibodies diffuse to the fiber walls and bind their specific ligands. Gautam et al 13 developed an anti-A antibody removal device that used novel synthetic blood group A antigens as the immobilized ligands. Using a mathematical model of antibody removal and in vitro anti-A capture data obtained in appropriately scaled-down modules, these studies indicated that a minimum antibody binding capacity of 0.0045 nmol/cm 2 would be required for a clinically effective device, which is five-to six-fold higher than the antibody binding capacity achieved based on our current immobilization methods.…”

Section: Introductionmentioning

confidence: 99%

“…Using a mathematical model of antibody removal and in vitro anti-A capture data obtained in appropriately scaled-down modules, these studies indicated that a minimum antibody binding capacity of 0.0045 nmol/cm 2 would be required for a clinically effective device, which is five-to six-fold higher than the antibody binding capacity achieved based on our current immobilization methods. 13 While efforts are ongoing to increase the immobilized antigen density of our current device, we are also developing a new antibody removal device based on integrated microfiltration fibers with antibody capturing beads distributed within the interstitial fiber space (BSAF device).…”

Section: Introductionmentioning

confidence: 99%

“…6,9,22,31 We have been developing antibody filtering devices designed for removal of antibodies directly from whole blood without the need for prior plasmapheresis. 2,13,18,19 In these devices, ligands specific to the targeted antibodies are immobilized on the luminal surfaces of dialyzer fibers configured into a module. Whole blood perfuses through the fibers and the targeted antibodies diffuse to the fiber walls and bind their specific ligands.…”

Section: Introductionmentioning

confidence: 99%

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Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules

Alikhani

Federspiel

2010

Ann Biomed Eng

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Anti-A/B antibody removal from blood reduces the hyperacute rejection risk following ABO-incompatible transplantation. We are developing an integrated bead and fiber module (BSAF) that selectively removes anti-A from blood. In BSAF blood flows through the inner lumen of microfiltration fibers. Starling flow carries plasma from the inner fiber lumen to the beads in the shell compartment where antibodies bind to covalently attached antigens on the beads. In this study, we developed a mathematical model to guide the choice of key design and operational parameters for a clinical BSAF device. The model demonstrated that for a given flow rate and reservoir volume, antibody removal rate was dependent on the magnitude of a lumped parameter, k (L) m (B)/Q (s), that characterizes the ratio of antibody uptake rate by the beads to the Starling flow rate in the device. The highest antibody removal rate was predicted for the perfusion limited regime, when k (L) m (B)/Q (s) → 10; Once this maximum limit was obtained, any further increase in the antibody removal rate was only possible by increasing the flow rate. Key model predictions were validated in a series of experiments. The model was then used to conceptually design a BSAF capable of a clinically relevant rate of anti-A removal.

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Section: Discussionmentioning

confidence: 99%

“…In each case, k L was calculated from fitting the reservoir antibody concentrations at various times to Eq. (13). The results of the fits of Eq.…”

Section: Measurement Of Model Parameters and Adsorption Capacity Of Mmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules

Alikhani

Federspiel

2010

Ann Biomed Eng

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High molecular weight blood group A trisaccharide‐polyacrylamide glycoconjugates as synthetic blood group A antigens for anti‐A antibody removal devices

et al. 2009

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Specific immunoadsorption of blood group antibodies by synthetic antigens immobilized on support matrices in the peri-transplantation period provides a promising solution to hyperacute rejection risk following ABO-incompatible transplantation. In this study, we investigated binding interactions between anti-A antibodies and synthetic blood group A trisaccharide conjugated with polyacrylamide of different molecular weights (30 and 1000 kDa). The glycopolymers were equipped with biotin tags and deposited on streptavidin-coated sensor chips. The affinity and kinetics of anti-A antibodies binding to glycoconjugates were studied using surface plasmon resonance (SPR). The high molecular weight conjugate (Atri-PAA1000-biotin) enhanced antibody binding capacity by two to three fold compared to the low molecular weight conjugate (Atri-PAA30-biotin), whereas varying the carbohydrate content in Atri-PAA1000-biotin (20 mol% or 50 mol%) did not affect antibody binding capacity of the glycoconjugate. The obtained results suggest that immunoadsorption devices, especially hollow fiber-based antibody filters which are limited in available surface area for antigen immobilization, may greatly benefit from the new synthetic high molecular weight polyacrylamide glycoconjugates.

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Specific antibody filter (SAF) binding capacity enhancement to remove anti‐A antibodies

et al. 2010

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Removal of Anti-A/B antibodies prior to ABO-incompatible transplantation can prevent hyperacute organ rejection. We are developing a specific antibody filter (SAF) device to selectively remove ABO blood group antibodies from the whole blood by utilizing immunoaffinity adsorption. The device consists of ultrafiltration hollow fiber membranes with synthetic antigens specific to bind blood group antibodies immobilized on the inner lumenal walls of the fibers. The aim of this study was to evaluate the effect of antigen molecular weight and surface activation process to increase the antibody binding capacity of the fiber membrane surface. A new higher molecular weight antigen Atri-pNSA-1000 compared with Atri-pNPA-30 (A-trisaccharide (Atri) conjugated to activated polymers of Mol. wt. 1000 kDa and 30 kDa, respectively) was employed to improve accessibility of the antigen to bind antibodies. Also, a cyanogen bromide (CNBr) based surface activation method mediated by TEA in neutral pH medium was used to enhance the number of active sites for antigen binding compared to a strong basic medium of NaOH. Using a CNBr/TEA activation method and by immobilizing Atri-pNSA-1000 antigen, an antibody binding capacity (∼0.01 monoclonal anti-A IgM nmol/cm(2)) was achieved on the fiber surface. This binding capacity was sufficient to reduce monoclonal antibody titer from 1:128 to final titer below 1:4 with a surface area to volume ratio that is similar to commercial dialysis device (∼1.1 m(2) surface area for an average body blood volume of 5 L).

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Monoclonal anti‐A antibody removal by synthetic A antigen immobilized on specific antibody filters

Cited by 4 publications

References 43 publications

Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules

Theoretical and Experimental Analysis of Anti-A Antibody Capture in Novel Integrated Bead and Hollow Fiber Modules

High molecular weight blood group A trisaccharide‐polyacrylamide glycoconjugates as synthetic blood group A antigens for anti‐A antibody removal devices

Specific antibody filter (SAF) binding capacity enhancement to remove anti‐A antibodies

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