Dose Levels in Particulate-Containing Formulations Impact Anti-drug Antibody Responses to Murine Monoclonal Antibody in Mice

Shomali, Maliheh; Tanriverdi, Sultan; Freitag, Angelika; Engert, Julia; Winter, Gerhard; Siedler, Michael; Kaymakcalan, Zehra; Carpenter, John F.; Randolph, Theodore W.

doi:10.1002/jps.24413

Cited by 30 publications

(22 citation statements)

References 39 publications

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“…21 The immunogenicity of a murine anti-TNFα IgG2c/κ antibody in mice was enhanced when the protein was adsorbed to the surfaces of micron-sized glass or aluminum hydroxide microparticles, or to the surface of micron-sized silicone oil droplets. 27 The antibody showed minimal conformational change upon adsorption to glass or aluminum hydroxide, 43 but was still immunogenic. Most recently, an emulsion of silicone oil droplets added to an ovalbumin formulation was shown to enhance immune responses to the adsorbed protein (in the absence of surfactant).…”

Section: Effects Of Product-related Factors On Immunogenicitymentioning

confidence: 99%

“…27,28,43 These models have been useful for investigations on the relative impacts of product-related factors on immunogenicity, as well as immune mechanisms involved in the breaking of immune tolerance (for a description of the concept of immune tolerance, see Goodnow et al 44 ). A practical advantage of this approach is that the mice in principle are suitable for testing the immunogenicity of any murine protein.…”

Section: Choice Of Mouse Modelmentioning

confidence: 99%

“…In a study using murine IgG, low doses of aggregated protein adsorbed to the surface of non-proteinaceous microparticles or silicone oil droplets provoked stronger immune responses in mice than higher doses. 27 Similarly, repeated administration of high doses of IgG-coated microparticles resulted in significantly lower ADA responses as compared to low doses. 21 These results highlight that it is challenging to choose an appropriate dosing schedule in murine models for evaluating immunogenicity of therapeutic proteins.…”

Section: Treatment Regimen Affects Immunogenicitymentioning

confidence: 99%

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Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Jiskoot

Kijanka

Randolph

et al. 2016

Journal of Pharmaceutical Sciences

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The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.

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Section: Effects Of Product-related Factors On Immunogenicitymentioning

confidence: 99%

Section: Choice Of Mouse Modelmentioning

confidence: 99%

Section: Treatment Regimen Affects Immunogenicitymentioning

confidence: 99%

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Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Jiskoot

Kijanka

Randolph

et al. 2016

Journal of Pharmaceutical Sciences

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“…[5][6][7][8][9][10][11] This cascade of interfacial molecular events may cause loss of bioactivity, anti-drug antibody response and, potentially, immunogenicity. 12,13 Addition of nonionic surfactants into mAb formulations is widely thought to inhibit protein adsorption. Many studies including our work have already shown that nonionic surfactants can prevent protein adsorption at the air/water interface when their concentrations are sufficiently high, 14,15 but it is also important to understand how they can influence mAb adsorption at the solid/water interface.…”

Section: Introductionmentioning

confidence: 99%

Coadsorption of a Monoclonal Antibody and Nonionic Surfactant at the SiO₂/Water Interface

Pan

et al. 2018

ACS Appl. Mater. Interfaces

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ZL and FP made equal contributions AbstractDuring the formulation of therapeutic monoclonal antibodies (mAbs), nonionic surfactants are commonly added to attenuate structural rearrangement caused by adsorption/desorption at interfaces during processing, shipping and storage. We examined the adsorption of a mAb (COE-3) at the SiO 2 /water interface in the presence of pentaethylene glycol monododecyl ether (C 12 E 5 ), polysorbate 80 (PS80-20EO) and a polysorbate 80 analogue with 7 ethoxylates (PS80-7EO). Spectroscopic ellipsometry (SE) was used to follow COE-3 dynamic adsorption and neutron reflection (NR) was used to determine interfacial structure and composition.Neither PS80-20EO nor C 12 E 5 had a notable affinity for COE-3 or the interface under the conditions studied, and thus did not prevent COE-3 adsorption. In contrast, PS80-7EO did coadsorb but did not influence the dynamic process or the equilibrated amount of absorbed COE-3. Near equilibration, COE-3 underwent structural rearrangement and PS80-7EO started to bind the COE-3 interfacial layer and subsequently formed a well-defined surfactant bilayer via self-assembly. The resultant interfacial layer was comprised of an inner mAb layer of some 70 Å thick and an outer surfactant layer of a further 70 Å, with distinct transitional regions across the mAb-surfactant and surfactant-bulk water boundaries. Once formed, such interfacial layers were very robust and worked to prevent further mAb adsorption, desorption and structural rearrangement. Such robust interfacial layers could be anticipated to exist for formulated mAbs stored in type II glass vials; further research is required to understand the behaviour of these layers for siliconized glass syringes.

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“…39 Another study reported that BALB/c mice (which do not produce IgG2c antibodies) exhibited enhanced immune responses when the mice were injected with a murine monoclonal IgG2c antibody in a formulation that contained silicone oil microdroplets. 40 …”

Section: Introductionmentioning

confidence: 99%

Silicone Oil Microdroplets Can Induce Antibody Responses Against Recombinant Murine Growth Hormone in Mice

Chisholm

Baker

Soucie

et al. 2016

Journal of Pharmaceutical Sciences

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Therapeutic protein products can cause adverse immune responses in patients. The presence of sub-visible particles is a potential contributing factor to the immunogenicity of parenterally-administered therapeutic protein formulations. Silicone oil microdroplets, which derive from silicone oil used as a lubricating coating on barrels of prefilled glass syringes, are often found in formulations. In this study, we investigated the potential of silicone oil microdroplets to act as adjuvants to induce an immune response in mice against a recombinant murine protein. Antibody responses in mice to subcutaneous injections of formulations of recombinant murine growth hormone (rmGH) that contained silicone oil microdroplets were measured and compared to responses to oil-free rmGH formulations. When rmGH formulations containing silicone oil microdroplets were administered once every other week, anti-rmGH antibodies were not detected. In contrast, mice exhibited a small IgG1 response against rmGH when silicone oil-containing rmGH formulations were administered daily, and an anti-rmGH IgM response was observed at later time points. Our findings showed that silicone oil microdroplets can act as an adjuvant to promote a break in immunological tolerance and induce antibody responses against a recombinant self-protein.

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Dose Levels in Particulate-Containing Formulations Impact Anti-drug Antibody Responses to Murine Monoclonal Antibody in Mice

Cited by 30 publications

References 39 publications

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Coadsorption of a Monoclonal Antibody and Nonionic Surfactant at the SiO₂/Water Interface

Silicone Oil Microdroplets Can Induce Antibody Responses Against Recombinant Murine Growth Hormone in Mice

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Dose Levels in Particulate-Containing Formulations Impact Anti-drug Antibody Responses to Murine Monoclonal Antibody in Mice

Cited by 30 publications

References 39 publications

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Coadsorption of a Monoclonal Antibody and Nonionic Surfactant at the SiO2/Water Interface

Silicone Oil Microdroplets Can Induce Antibody Responses Against Recombinant Murine Growth Hormone in Mice

Contact Info

Product

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About

Coadsorption of a Monoclonal Antibody and Nonionic Surfactant at the SiO₂/Water Interface