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22 results on '"Seki, Takuya"'

2. AJICAP-M: Traceless Affinity Peptide Mediated Conjugation Technology for Site-Specific Antibody-Drug Conjugate Synthesis

Author

Matsuda, Yutaka, primary, Shikida, Natsuki, additional, Hatada, Noriko, additional, Yamada, Kei, additional, Seki, Takuya, additional, Nakahara, Yuichi, additional, Endo, Yuta, additional, Shimbo, Kazutaka, additional, Takahashi, Kazutoshi, additional, Nakayama, Akira, additional, Mendelsohn, Brian A., additional, Fujii, Tomohiro, additional, Okuzumi, Tatsuya, additional, and Hirasawa, Shigeo, additional

Published
2024
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6. Bispecific Antibodies Produced via Chemical Site-Specific Conjugation Technology: AJICAP Second-Generation

Author

Fujii, Tomohiro, primary, Ito, Kenichiro, additional, Takahashi, Kazutoshi, additional, Aoki, Tsubasa, additional, Takasugi, Rika, additional, Seki, Takuya, additional, Iwai, Yusuke, additional, Watanabe, Tomohiro, additional, Hirama, Ryusuke, additional, Tsumura, Ryo, additional, Fuchigami, Hirobumi, additional, Yasunaga, Masahiro, additional, and Matsuda, Yutaka, additional

Published
2023
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7. AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody–Drug Conjugate Production

Author

Fujii, Tomohiro, primary, Matsuda, Yutaka, additional, Seki, Takuya, additional, Shikida, Natsuki, additional, Iwai, Yusuke, additional, Ooba, Yuri, additional, Takahashi, Kazutoshi, additional, Isokawa, Muneki, additional, Kawaguchi, Sayaka, additional, Hatada, Noriko, additional, Watanabe, Tomohiro, additional, Takasugi, Rika, additional, Nakayama, Akira, additional, Shimbo, Kazutaka, additional, Mendelsohn, Brian A., additional, Okuzumi, Tatsuya, additional, and Yamada, Kei, additional

Published
2023
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10. Chemical Site-Specific Conjugation Platform to Improve the Pharmacokinetics and Therapeutic Index of Antibody–Drug Conjugates

Author

Matsuda, Yutaka, primary, Seki, Takuya, additional, Yamada, Kei, additional, Ooba, Yuri, additional, Takahashi, Kazutoshi, additional, Fujii, Tomohiro, additional, Kawaguchi, Sayaka, additional, Narita, Takahiro, additional, Nakayama, Akira, additional, Kitahara, Yoshiro, additional, Mendelsohn, Brian A., additional, and Okuzumi, Tatsuya, additional

Published
2021
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12. Evaluation of a Novel Boron-Containing α-d-Mannopyranoside for BNCT

Author

Tsurubuchi, Takao, primary, Shirakawa, Makoto, additional, Kurosawa, Wataru, additional, Matsumoto, Kayo, additional, Ubagai, Risa, additional, Umishio, Hiroshi, additional, Suga, Yasuyo, additional, Yamazaki, Junko, additional, Arakawa, Akihiro, additional, Maruyama, Yutaka, additional, Seki, Takuya, additional, Shibui, Yusuke, additional, Yoshida, Fumiyo, additional, Zaboronok, Alexander, additional, Suzuki, Minoru, additional, Sakurai, Yoshinori, additional, Tanaka, Hiroki, additional, Nakai, Kei, additional, Ishikawa, Eiichi, additional, and Matsumura, Akira, additional

Published
2020
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16. AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody–Drug Conjugate Production

Author

Fujii, Tomohiro, Matsuda, Yutaka, Seki, Takuya, Shikida, Natsuki, Iwai, Yusuke, Ooba, Yuri, Takahashi, Kazutoshi, Isokawa, Muneki, Kawaguchi, Sayaka, Hatada, Noriko, Watanabe, Tomohiro, Takasugi, Rika, Nakayama, Akira, Shimbo, Kazutaka, Mendelsohn, Brian A., Okuzumi, Tatsuya, and Yamada, Kei

Abstract

The site-directed chemical conjugation of antibodies remains an area of great interest and active efforts within the antibody–drug conjugate (ADC) community. We previously reported a unique site modification using a class of immunoglobulin-G (IgG) Fc-affinity reagents to establish a versatile, streamlined, and site-selective conjugation of native antibodies to enhance the therapeutic index of the resultant ADCs. This methodology, termed “AJICAP”, successfully modified Lys248 of native antibodies to produce site-specific ADC with a wider therapeutic index than the Food and Drug Administration-approved ADC, Kadcyla. However, the long reaction sequences, including the reduction–oxidation (redox) treatment, increased the aggregation level. In this manuscript, we aimed to present an updated Fc-affinity-mediated site-specific conjugation technology named “AJICAP second generation” without redox treatment utilizing a “one-pot” antibody modification reaction. The stability of Fc affinity reagents was improved owing to structural optimization, enabling the production of various ADCs without aggregation. In addition to Lys248 conjugation, Lys288 conjugated ADCs with homogeneous drug-to-antibody ratio of 2 were produced using different Fc affinity peptide reagent possessing a proper spacer linkage. These two conjugation technologies were used to produce over 20 ADCs from several combinations of antibodies and drug linkers. The in vivoprofile of Lys248 and Lys288 conjugated ADCs was also compared. Furthermore, nontraditional ADC production, such as antibody–protein conjugates and antibody–oligonucleotide conjugates, were achieved. These results strongly indicate that this Fc affinity conjugation approach is a promising strategy for manufacturing site-specific antibody conjugates without antibody engineering.

Published
2024
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