Antibody Responses in Mice to Particles Formed from Adsorption of a Murine Monoclonal Antibody onto Glass Microparticles

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

doi:10.1002/jps.23772

Cited by 24 publications

(30 citation statements)

References 52 publications

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“…23 The occurrence of isotype switching in other immune-tolerant mouse models also provides evidence of the involvement of T-helper cells in the breaking of immune tolerance. 24,26,28,32,43 Moreover, the timing of T-cell recruitment and the number of germinal centers formed after administration of aggregated rhIFNβ-1b were almost identical in immune-tolerant and wild-type mice. 69 Nevertheless, there are several indications that the breaking of immune tolerance occurs via mechanisms that differ from a classical immune response against foreign antigens.…”

Section: Immune Mechanisms Are Not Yet Fully Understoodmentioning

confidence: 93%

“…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%

“…The choice of the mouse strain is of great importance, as the immune response is strongly dependent on the strain. 38,43,46 For instance, BALB/c and C57BL/6 mice differ in their immunological and functional architecture and their sensitivity to antigenic stimuli. In BALB/c mice, T-cell functionality and the cytokine release capability is much higher than in C57BL/6 mice, making BALB/c mice better models for studying adaptive phase responses.…”

Section: Choice Of Mouse Modelmentioning

confidence: 99%

“…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%

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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: Immune Mechanisms Are Not Yet Fully Understoodmentioning

confidence: 93%

Section: Choice Of Mouse Modelmentioning

confidence: 99%

Section: Choice Of Mouse Modelmentioning

confidence: 99%

Section: Effects Of Product-related Factors On Immunogenicitymentioning

confidence: 99%

See 2 more Smart Citations

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Jiskoot

Kijanka

Randolph

et al. 2016

Journal of Pharmaceutical Sciences

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“…Mice administered with rmGH alone did not produce IgM at later time points. In another study, Shomali et al 15 also observed increased IgM levels at later times in mice subcutaneously injected with formulations of a murine monoclonal antibody adsorbed to glass microparticles. It is unclear why IgM antibodies appear against rmGH only at later time points.…”

Section: Discussionmentioning

confidence: 88%

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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