Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

Hang, Bich; Kang, Hyo Jeong; Song, Jung A.; Nguyen, Minh Tan; Park, Sangsu; Yoo, Jiwon; Nguyễn, Anh Ngọc; Kwon, Grace G.; Jang, Jaepyeong; Jang, Mi; Lee, Sun-Ju; So, Seoungjun; Sim, Seongrak; Lee, Kyung Jin; Osborn, Mark J.; Choe, Han

doi:10.1038/s41598-017-06726-7

Cited by 17 publications

(19 citation statements)

References 31 publications

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“…Studies have shown that single injections of PEG-rhG-CSF were at least as potent as multiple injections of rhG-CSF in treating neutropenia [42]. Fusion of rhG-CSF to an Fc receptor [43] or serum albumin [44,45] was effective in increasing half-life of rhG-CSF and thus mobilization efficiency. In all of these studies, plasma levels of rhG-CSF were considered to be a marker for effectiveness of the modification.…”

Section: Discussionmentioning

confidence: 99%

Albumin Modifies Responses to Hematopoietic Stem Cell Mobilizing Agents in Mice

Danner

Bönig

Wiercinska

2019

Cells

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Albumin, the most abundant plasma protein, not only controls osmotic blood pressure, but also serves as a carrier for various small molecules, including pharmaceuticals. Its impact on pharmacological properties of many drugs has been extensively studied over decades. Here, we focus on its interaction with the following mobilizing agents: Granulocyte-colony stimulating factor (G-CSF) and AMD3100, where such analyses are lacking. These compounds are widely used for hematopoietic stem cell mobilization of healthy donors or patients. Using albumin-deficient (Alb−/−) mice, we studied the contribution of albumin to mobilization outcomes. Mobilization with the bicyclam CXCR4 antagonist AMD3100 was attenuated in Alb−/− mice compared to wild-type littermates. By contrast, mobilization with recombinant human G-CSF (rhG-CSF), administered twice daily over a five-day course, was significantly increased in Alb−/− mice. In terms of a mechanism, we show that rhG-CSF bioavailability in the bone marrow is significantly improved in Alb−/− mice, compared to wild-type (WT) littermates, where rhG-CSF levels dramatically drop within a few hours of the injection. These observations likely explain the favorable mobilization outcomes with split-dose versus single-dose administration of rhG-CSF to healthy donors.

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Section: Discussionmentioning

confidence: 99%

Albumin Modifies Responses to Hematopoietic Stem Cell Mobilizing Agents in Mice

Danner

Bönig

Wiercinska

2019

Cells

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“…103 Choe and coworkers group attempted to address this issue through conjugation 20kDa PEG to the amine terminus of G-CSF. 104 The in vitro activity and the half maximal effective concentration (EC 50 ) of the conjugate and native protein samples were investigated through the incubation of mouse myelogenous leukemia cells which ultimately showed similar activity suggesting pegylation does not negatively impact biological activity of G-CSF. The in vivo activity was determined via the injection of the native and conjugated protein into neutropenic rats (Fig 8).…”

Section: Recombinant Human Interferon-alpha (Ifn-α)-mentioning

confidence: 99%

Polymer conjugation of proteins as a synthetic post-translational modification to impact their stability and activity

2019

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“…In the case of antibody fragments, PEGylation has been shown to lengthen their circulating half-life, enhance their proteolytic resistance of therapeutic proteins, and reduce their immunogenicity. 27,29,41 Various PEGylation strategies have been studied for different therapeutic proteins, such as nonspecific PEGylation, thiol and bridging PEGylation, enzymatic PEGylation, and noncovalent PEGylation, 23,27…”

Section: Peg-s-fab Induces More Potent In Vivo Antitumor Activitymentioning

confidence: 99%

Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

Liu¹,

Deng²,

Xing³

et al. 2018

IJN

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IntroductionBispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies.Materials and methodsIn this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab.ResultsThe half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab.ConclusionThis study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies.

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Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

Cited by 17 publications

References 31 publications

Albumin Modifies Responses to Hematopoietic Stem Cell Mobilizing Agents in Mice

Albumin Modifies Responses to Hematopoietic Stem Cell Mobilizing Agents in Mice

Polymer conjugation of proteins as a synthetic post-translational modification to impact their stability and activity

Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

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