Akira Okazaki

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Depletion of fucose from human IgG1 oligosaccharide improves its affinity for Fcgamma receptor IIIa (FcgammaRIIIa). This is the first case where a glycoform modification is shown to improve glycoprotein affinity for the receptors without carbohydrate-binding capacity, suggesting a novel glyco-engineering strategy to improve ligand-receptor binding. To(More)
Antibody-dependent cellular cytotoxicity (ADCC) has recently been identified as one of the critical mechanisms underlying the clinical efficacy of therapeutic antibodies, especially anticancer antibodies. Therapeutic antibodies fully lacking the core fucose of the Fc oligosaccharides have been found to exhibit much higher ADCC in humans than their(More)
The structure of asparagine-linked oligosaccharides attached to the antibody constant region (Fc) of human immunoglobulin G1 (IgG1) has been shown to affect the pharmacokinetics and antibody effector functions of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, it is still unclear how differences in the(More)
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.(More)
Human leukocyte receptor IIIa (Fc gamma RIIIa) plays an important role in mediating therapeutic antibodies' antibody-dependent cellular cytotoxicity (ADCC), which is closely related to the clinical efficacy of anticancer processes in humans in vivo. The removal of the core fucose from oligosaccharides attached to the Fc region of antibodies improves Fc(More)
Mami Shibata-Koyama2, Shigeru Iida2, Akira Okazaki2, Katsuhiro Mori2, Kazuko Kitajima-Miyama2, Seiji Saitou2, Shingo Kakita2, Yutaka Kanda2, Kenya Shitara2, Koichi Kato3,4, and Mitsuo Satoh1,2 2Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd, 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533; 3Graduate School of Pharmaceutical Sciences, Nagoya City(More)
Currently, removal of core fucose from the Fc oligosaccharides of therapeutic antibodies is widely recognized as being of great importance for the effector function of antibody-dependent cellular cytotoxicity, and alpha-1,6-fucosyltransferase (FUT8) knockout cells have been generated as an ideal host cell line for manufacturing such therapeutics. Here, we(More)
Recent studies have shown that antibodies with low fucose content in their oligosaccharides exhibit highly potent antibody-dependent cellular cytotoxicity (ADCC). However, composites of therapeutic antibodies produced by conventional production systems using cell lines such as Chinese hamster ovary (CHO) and SP2/0 do not necessarily contain sufficient(More)
We present herein a case report of vanishing colon cancer with intussusception. A 70-year-old man with hematochezia was admitted to our hospital. Preoperative images showed ileus due to a colonic tumor. At operation, normograde intussusception without any tumor was recognized at the sigmoid colon. Interestingly, the regional lymph nodes were found to be(More)
BACKGROUND Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. METHOD There were 708 study subjects, all of whom had early breast cancer treated between 1992 and(More)