Non-fucosylated Therapeutic Antibodies: The Next Generation of Therapeutic Antibodies

Satoh, Mitsuo; Iida, Shigeru; Yamane-Ohnuki, Naoko; Mori, Keisuke; Kanda, Yutaka; Kuni-Kamochi, Reiko; Nakano, Ryoko; Imai-Nishiya, Harue; Okazaki, Akira; Shinkawa, Toyohide; Natsume, Akihito; Niwa, Rinpei; Shitara, Kenya

doi:10.1007/978-1-4020-9646-4_1

Cited by 15 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, considering that ADCC activity of antibodies can be enhanced by changing their glycosylation from a typical core fucosylated complex type to a structure lacking this core fucosylation (Nechansky et al, 2007;Shinkawa et al, 2003), the knock-out of the relevant fucosyltransferase(s), e.g. using the Potelligent ® technology (BioWa, Inc.) also seems reasonable (Beuger et al, 2009;Satoh et al, 2006), but has only been performed in mammalian cells. Indeed, realisation of a knock-out in "High Five" cells requires not just knowledge of the relevant gene sequence(s), but also develop- ment of the gene deletion technology in insect cells.…”

Section: Determination Of N-glycan Structuresmentioning

confidence: 99%

Insect cells for antibody production: Evaluation of an efficient alternative

Palmberger

Rendić

Tauber

et al. 2011

Journal of Biotechnology

View full text Add to dashboard Cite

Section: Determination Of N-glycan Structuresmentioning

confidence: 99%

Insect cells for antibody production: Evaluation of an efficient alternative

Palmberger

Rendić

Tauber

et al. 2011

Journal of Biotechnology

View full text Add to dashboard Cite

“…Deletion of a specific glycan or the modification of glycan chains with fucose or sialic acid enhances antibody-dependent cellular cytotoxity (ADCC) which is a key player in killing the cancer tissues (Satoh, Iida, & Shitara, 2006;Shields et al, 2002;Shinkawa et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Glycans and Cancer

Taniguchi

Kizuka

2015

Advances in Cancer Research

323

132

View full text Add to dashboard Cite

“…More importantly, the enhanced ADCC of nonfucosylated therapeutic antibodies against a specific antigen has been shown to be inhibited in a dosedependent manner by fucosylated antibodies against the same antigen in the case of both rituximab and trastuzumab in vitro and ex vivo Satoh et al 2006). Non-fucosylated therapeutic antibodies existing in the antibody mixtures, composed of non-fucosylated and fucosylated forms, do not exhibit activity equivalent to that of equal amounts of non-fucosylated therapeutic antibodies alone.…”

Section: Fucosylated Therapeutic Antibodies Spoil the Nonfucosylated mentioning

confidence: 96%

“…This phenomenon leads to the elucidation of necessity of the use of high doses in the clinical treatment, and also elucidates the molecular mechanism for the enhanced efficacy of non-fucosylated therapeutic antibodies in humans. Non-fucosylated therapeutic antibodies have much higher binding affinity for FccRIIIa than fucosylated human serum IgG, which is a preferable character to conquer the interference by human plasma IgG Satoh et al 2006). Therefore, non-fucosylated therapeutic antibodies can evade the inhibitory effect of human plasma IgG on ADCC through their high FccRIIIa bonding.…”

Section: Human Serum Igg Inhibits Therapeutic Antibodyinduced Adccmentioning

confidence: 98%

“…These include the introduction of amino acid mutations in the Fc region (Shields et al 2001;Lazar et al 2006) and the co-administration of CpG as an adjuvant (Jahrsdorfer and Weiner 2003;van Ojik et al 2003) or that of cytokines such as IL-2 (Friedberg et al 2002) and GM-CSF (Stockmeyer et al 2001). Among these efforts, the modification of N-linked Fc oligosaccharides, especially core-fucose removal, has been of note as a key of next generation therapeutic antibodies with improved efficacy (Shields et al 2002;Shinkawa et al 2003;Yamane-Ohnuki et al 2004;Mori et al 2004;Okazaki et al 2004;Niwa et al 2004aNiwa et al , b, 2005aNiwa et al , 2005bNatsume 2005;Jefferis 2005;Iida et al 2006;Kanda et al 2006;Satoh et al 2006).…”

Section: Current Feature Of Therapeutic Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies

et al. 2007

Self Cite

View full text Add to dashboard Cite

Therapeutic antibody IgG1 has two N-linked oligosaccharide chains bound to the Fc region. The oligosaccharides are of the complex biantennary type, composed of a trimannosyl core structure with the presence or absence of core fucose, bisecting N-acetylglucosamine (GlcNAc), galactose, and terminal sialic acid, which gives rise to structural heterogeneity. Both human serum IgG and therapeutic antibodies are well known to be heavily fucosylated. Recently, antibody-dependent cellular cytotoxicity (ADCC), a lytic attack on antibody-targeted cells, has been found to be one of the critical effector functions responsible for the clinical efficacy of therapeutic antibodies such as anti-CD20 IgG1 rituximab (Rituxan((R))) and anti-Her2/neu IgG1 trastuzumab (Herceptin((R))). ADCC is triggered upon the binding of lymphocyte receptors (FcgammaRs) to the antibody Fc region. The activity is dependent on the amount of fucose attached to the innermost GlcNAc of N-linked Fc oligosaccharide via an alpha-1,6-linkage, and is dramatically enhanced by a reduction in fucose. Non-fucosylated therapeutic antibodies show more potent efficacy than their fucosylated counterparts both in vitro and in vivo, and are not likely to be immunogenic because their carbohydrate structures are a normal component of natural human serum IgG. Thus, the application of non-fucosylated antibodies is expected to be a powerful and elegant approach to the design of the next generation therapeutic antibodies with improved efficacy. In this review, we discuss the importance of the oligosaccharides attached to the Fc region of therapeutic antibodies, especially regarding the inhibitory effect of fucosylated therapeutic antibodies on the efficacy of non-fucosylated counterparts in one medical agent. The impact of completely non-fucosylated therapeutic antibodies on therapeutic fields will be also discussed.

show abstract

Non-fucosylated Therapeutic Antibodies: The Next Generation of Therapeutic Antibodies

Cited by 15 publications

References 41 publications

Insect cells for antibody production: Evaluation of an efficient alternative

Insect cells for antibody production: Evaluation of an efficient alternative

Glycans and Cancer

Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies

Contact Info

Product

Resources

About