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8 results on '"Kubo, Chiyomi"'

1. Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+ T cell interleukin-2 secretion

Author

Arata, Yoshiyuki, primary, Motoyama, Shigeki, additional, Yano, Mariko, additional, Ikuno, Tatsuya, additional, Ito, Shunsuke, additional, Matsushita, Tomochika, additional, Takeiri, Akira, additional, Nishito, Yukari, additional, Yabuki, Nami, additional, Mizuno, Hideaki, additional, Sampei, Zenjiro, additional, Mishima, Masayuki, additional, Honda, Masaki, additional, Kiyokawa, Jumpei, additional, Suzuki, Hiromi, additional, Chiba, Shuichi, additional, Tabo, Mitsuyasu, additional, and Kubo, Chiyomi, additional

Published
2023
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2. Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+ T cell interleukin-2 secretion.

Author

Arata, Yoshiyuki, Motoyama, Shigeki, Yano, Mariko, Ikuno, Tatsuya, Ito, Shunsuke, Matsushita, Tomochika, Takeiri, Akira, Nishito, Yukari, Yabuki, Nami, Mizuno, Hideaki, Sampei, Zenjiro, Mishima, Masayuki, Honda, Masaki, Kiyokawa, Jumpei, Suzuki, Hiromi, Chiba, Shuichi, Tabo, Mitsuyasu, and Kubo, Chiyomi

Published
2023
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4. MHC-associated peptide proteomics enabling highly sensitive detection of immunogenic sequences for the development of therapeutic antibodies with low immunogenicity

Author

Sekiguchi, Nobuo, primary, Kubo, Chiyomi, additional, Takahashi, Ayako, additional, Muraoka, Kumiko, additional, Takeiri, Akira, additional, Ito, Shunsuke, additional, Yano, Mariko, additional, Mimoto, Futa, additional, Maeda, Atsuhiko, additional, Iwayanagi, Yuki, additional, Wakabayashi, Tetsuya, additional, Takata, Shotaro, additional, Murao, Naoaki, additional, Chiba, Shuichi, additional, and Ishigai, Masaki, additional

Published
2018
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5. Rapid in vitroassessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+T cell interleukin-2 secretion

Author

Arata, Yoshiyuki, Motoyama, Shigeki, Yano, Mariko, Ikuno, Tatsuya, Ito, Shunsuke, Matsushita, Tomochika, Takeiri, Akira, Nishito, Yukari, Yabuki, Nami, Mizuno, Hideaki, Sampei, Zenjiro, Mishima, Masayuki, Honda, Masaki, Kiyokawa, Jumpei, Suzuki, Hiromi, Chiba, Shuichi, Tabo, Mitsuyasu, and Kubo, Chiyomi

Abstract

ABSTRACTTherapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4+T cells induced by therapeutic antibodies. IL-2-secreting CD4+T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.

Published
2023
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8. Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4 + T cell interleukin-2 secretion.

Author

Arata Y, Motoyama S, Yano M, Ikuno T, Ito S, Matsushita T, Takeiri A, Nishito Y, Yabuki N, Mizuno H, Sampei Z, Mishima M, Honda M, Kiyokawa J, Suzuki H, Chiba S, Tabo M, and Kubo C

Subjects
Leukocytes, Mononuclear metabolism, Cytokines metabolism, CD4-Positive T-Lymphocytes, T-Lymphocytes, Interleukin-2 pharmacology
Abstract

Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4 + T cells induced by therapeutic antibodies. IL-2-secreting CD4 + T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.

Published
2023
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