Differences between IGIV products: Impact on clinical outcome

Gelfand, Erwin W.

doi:10.1016/j.intimp.2005.11.003

Cited by 92 publications

(74 citation statements)

References 15 publications

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“…Different IVIg preparations are frequently treated as interchangeable products clinically, but it is well-known that significant differences in product preparations exist that may impact tolerability and activity in selected clinical applications (9). At the current maximal dosing regimens, only partial and unsustained responses are obtained in many instances (2,4).…”

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confidence: 99%

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

Washburn

Schwab

Ortiz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

201

161

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Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc-sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity.IVIg | sialylation | antibody | inflammation | autoimmune disease

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mentioning

confidence: 99%

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

Washburn

Schwab

Ortiz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

201

161

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“…In clinical practice, different preparations of IVIG or different batches may result in variable beneficial effects. For a biological study, it is therefore very important to describe the reasons for choosing a preparation of IVIG and to consider the specific characteristics of the product that are relevant to a particular clinical response (Elluru et al, 2006;Gelfand, 2006;Gürcan, Keskin, Ahmed, 2010).…”

Section: Resultsmentioning

confidence: 99%

“…In the IVIG produced, consumption of the complement was not greater than 50%, as required by the European Pharmacopoeia. The product was kept at pH 4.0 -4.5, which is optimal for maintaining IgG in an unaggregated state (Gelfand, 2006). Initially developed to produce a stable IgG solution, a low pH formulation was also used to achieve a final step involving inactivation of the virus.…”

Section: Resultsmentioning

confidence: 99%

Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

Gouveia

Oliveira

Lucena³

et al. 2013

Braz. J. Pharm. Sci.

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Dengue represents an important health problem in Brazil and therefore there is a great need to develop a vaccine or treatment. The neutralization of the dengue virus by a specific antibody can potentially be applied to therapy. The present paper describes, for the first time, the preparation of Immunoglobulin specific for the dengue virus (anti-DENV IgG), collected from screened Brazilian blood-donations. Production was performed using the classic Cohn-Oncley process with minor modifications. The anti-DENV IgG was biochemically and biophysically characterized and fulfilled the requirements defined by the European Pharmacopoeia. The finished product was able to neutralize different virus serotypes (DENV-1, DENV-2, and DENV-3), while a commercial IgG collected from American blood donations was found to have low anti-dengue antibody titers. Overall, this anti-DENV IgG represents an important step in the study of the therapeutic potential and safety of a specific antibody that neutralizes the dengue virus in humans.Uniterms:. Viral infections. Dengue/treatment. Dengue/virus/neutralization. Immunoglobulins/ preparation. Plasma fractionation. Virus neutralization.A dengue representa um importante problema de saúde no Brasil, portanto, a identificação de vacina ou tratamento eficaz é uma necessidade urgente. A neutralização do vírus da dengue, por anticorpo específico, tem potencial aplicação terapêutica. Descrevemos aqui, pela primeira vez, a preparação de imunoglobulina específica para o vírus da dengue (IgG anti-DENV), produzida a partir do plasma selecionado de doadores brasileiros. A produção foi realizada utilizando o método clássico de Cohn-Oncley com pequenas modificações. A IgG anti-DENV foi bioquimicamente e biofisicamente caracterizada e cumpriu os requisitos definidos pela Farmacopeia Europeia. O produto final foi capaz de neutralizar diferentes sorotipos do vírus (DENV-1, DENV-2 e DENV-3), enquanto que a IgG comercial, produzida a partir do plasma de doadores americanos, apresentou baixos títulos de anticorpos anti-dengue. No geral, esta IgG anti-DENV representa uma importante etapa para o estudo do potencial terapêutico e segurança da neutralização, por anticorpos específicos, do vírus da dengue em humanos.Unitermos: Infecções virais. Dengue/tratamento. Dengue/vírus/neutralização. Imunoglobulinas específicas/preparação. Fracionamento de plasma. Neutralização viral. INTRODUCTIONThere are around 2.5 billion people living in areas endemic for dengue fever and it is estimated that there are 100 million infections annually (Gubler 1998). The burden of dengue in endemic countries weighs heaviest on children. However, there has been an increasing trend towards adult infection in certain countries (Ooi, Goh, Gubler, 2006;Cummings et al., 2009). Most travelers with dengue have been adults (Wilder-Smith, Schwartz, 2005). Currently, neither cure nor vaccines are available, and new therapies are thus urgently needed. Although there have been considerable developments in medicinal chemistry, no promising small-organic...

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“…Restriction to high-quality studies with a low risk of confounding factors did not show any benefit from IVIG administration with both standard and IgMenriched preparations [10]. Most importantly, the heterogeneous quality of IVIG preparations may represent a major but non-measurable bias across studies [13]. The main conclusion from the meta-analysis was that the current evidence for benefits was inconsistent and inconclusive, and indeed the latest version of the Surviving Sepsis Campaign guidelines in 2012 stated: ''we suggest not using intravenous immunoglobulins in adult patients with severe sepsis or septic shock (grade 2B)'' [14].…”

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confidence: 93%