High Shear Rheology and Anisotropy in Concentrated Solutions of Monoclonal Antibodies

Zarraga, Isidro E.; Taing, Rosalynn; Zarzar, Jonathan; Luoma, Jacob; Hsiung, Jenny; Patel, Ankit R.; Lim, Fredric J.

doi:10.1002/jps.23647

Cited by 54 publications

(49 citation statements)

References 32 publications

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“…The high-affinity interaction between the His-Tag on the EAKIIH6 and the anti-His IgG served as a molecular bridge to anchor the Epcam-expressing TECs on the EAK16-II/EAKIIH6 structure. With similar adaptor design, we have previously shown that the In the current study, viscosity the self-assembling peptide EAK16-II that forms the material network was measured using capillary rheometry [14]. This method determines viscosity by measuring pressure difference as sample thrusts through microfluidic channels, without an air-liquid interface as a potential confounding factor.…”

Section: Eak16-ii/eakiih6 Mediated the Formation Of Mini-thymus Complmentioning

confidence: 85%

Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel

Tajima

Liu

Pradhan

et al. 2015

Clinical Immunology

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Herein, we highlight the technical feasibility of generating a functional mini thymus with a novel hydrogel system, based on a peptide-based self-assembly platform that can induce the formation of 3-D thymic epithelial cell (TEC) clusters. Amphiphilic peptide EAK16-II co-assembled with its histidinylated analogue EAKIIH6 into beta-sheet fibrils. When adaptor complexes (recombinant protein A/G molecules loaded with both anti-His and anti-EpCAM IgGs) were added to the mix, TECs were tethered to the hydrogel and formed 3-D mini clusters. TECs bound to the hydrogel composites retained their molecular properties; and when transplanted into athymic nude mice, they supported the development of functional T-cells. These mini thymic units of TECs can be useful in clinical applications to reconstitute T-cell adaptive immunity.

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Section: Eak16-ii/eakiih6 Mediated the Formation Of Mini-thymus Complmentioning

confidence: 85%

Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel

Tajima

Liu

Pradhan

et al. 2015

Clinical Immunology

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“…Therefore, we adopt a viscosity model for a semi-dilute polymer solution. 26 The viscosity is proportional to the product of the elastic modulus G and the longest relaxation time τ, 27 which takes the following form in the semi-dilute regime [28][29][30] …”

Section: Modelmentioning

confidence: 99%

Entanglement Model of Antibody Viscosity

Schmit

Mishra

et al. 2014

J. Phys. Chem. B

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Antibody solutions are typically much more viscous than solutions of globular proteins at equivalent volume fraction. Here we propose that this is due to molecular entanglements that are caused by the elongated shape and intrinsic flexibility of antibody molecules. We present a simple theory in which the antibodies are modeled as linear polymers that can grow via reversible bonds between the antigen binding domains. This mechanism explains the observation that relatively subtle changes to the interparticle interaction can lead to large changes in the viscosity. The theory explains the presence of distinct power law regimes in the concentration dependence of the viscosity as well as the correlation between the viscosity and the charge on the variable domain in our anti-streptavidin IgG 1 model system.

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“…To characterize the effect of mixing dL5_EAK and EAK16-II, the viscosities of solutions containing both were measured using capillary rheometry by which pressure gradient of the sample is measured across microfluidic channels [42]. Consistent with results reported by the Chen group [43], viscosity of diluted EAK16-II peaked at approximately 25% PBS (Supplemental material S2), indicating that the method is sensitive to the same material behavior of the βFP.…”

Section: Resultsmentioning

confidence: 89%

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

Liu

Saunders

Bagia

et al. 2016

Journal of Controlled Release

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Herein we report an injectable film by which antibodies can be localized in vivo. The system builds upon a bifunctional polypeptide consisting of a fluorogen-activating protein (FAP) and a β-fibrillizing peptide (βFP). The FAP domain generates fluorescence that reflects IgG binding sites conferred by Protein A/G (pAG) conjugated with the fluorogen malachite green (MG). A film is generated by mixing these proteins with molar excess of EAK16-II, a βFP that forms β-sheet fibrils at high salt concentrations. The IgG-binding, fluorogenic film can be injected in vivo through conventional needled syringes. Confocal microscopic images and dose–response titration experiments showed that loading of IgG into the film was mediated by pAGMG bound to the FAP. Release of IgG in vitro was significantly delayed by the bioaffinity mechanism; 26% of the IgG were released from films embedded with pAGMG after five days, comparedto close to 90% in films without pAGMG. Computational simulations indicated that the release rate of IgG is governed by positive cooperativity due to pAGMG. When injected into the subcutaneous space of mouse footpads, film-embedded IgG were retained locally, with distribution through the lymphatics impeded. The ability to track IgG binding sites and distribution simultaneously will aid the optimization of local antibody delivery systems.

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High Shear Rheology and Anisotropy in Concentrated Solutions of Monoclonal Antibodies

Cited by 54 publications

References 32 publications

Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel

Bioengineering mini functional thymic units with EAK16-II/EAKIIH6 self-assembling hydrogel

Entanglement Model of Antibody Viscosity

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein

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