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29 results on '"Sampei, Zenjiro"'

1. A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a nonhemophilic state

Author

Teranishi-Ikawa, Yuri, Soeda, Tetsuhiro, Koga, Hikaru, Yamaguchi, Kazuki, Kato, Kazuki, Esaki, Keiko, Asanuma, Kentaro, Funaki, Miho, Ichiki, Mina, Ikuta, Yuri, Ito, Shunsuke, Joyashiki, Eri, Komatsu, Shun-Ichiro, Muto, Atsushi, Nishimura, Kei, Okuda, Momoko, Sanada, Hisakazu, Sato, Motohiko, Shibahara, Norihito, Wakabayashi, Tetsuya, Yamaguchi, Koji, Matsusaki, Akiko, Sampei, Zenjiro, Shiraiwa, Hirotake, Konishi, Hiroko, Kawabe, Yoshiki, Hattori, Kunihiro, Kitazawa, Takehisa, and Igawa, Tomoyuki

Published
2024
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2. Beyond Recycling Antibodies: Crovalimab's Molecular Design Enables Four-Weekly Subcutaneous Injections for PNH Treatment.

Author

Sampei, Zenjiro, Haraya, Kenta, Gan, Siok Wan, Muraoka, Masaru, Hayasaka, Akira, Fukuzawa, Taku, Shida-Kawazoe, Meiri, Tsuboi, Yoshinori, Gotoh, Akihiko, Obara, Naoshi, and Ueda, Yasutaka

Subjects
*PAROXYSMAL hemoglobinuria, *SUBCUTANEOUS injections, *SINGLE nucleotide polymorphisms, *INTRAVENOUS therapy, *IMMUNOTECHNOLOGY
Abstract

The advent of recycling antibodies, leveraging pH-dependent antigen binding and optimized FcRn interaction, has advanced the field of antibody therapies, enabling extended durability and reduced dosages. Eculizumab (Soliris®) demonstrated the efficacy of C5 inhibitors for paroxysmal nocturnal hemoglobinuria (PNH), while its derivative, ravulizumab (Ultomiris®), recognized as a recycling antibody, extended the dosing intervals. However, limitations including intravenous administration and inefficacy in patients with the R885H single-nucleotide polymorphism (SNP) in C5 could necessitate alternative solutions. Crovalimab (PiaSky®), a next-generation recycling antibody, overcomes these challenges with innovative charge engineering, achieving the enhanced cellular uptake of C5–crovalimab complexes and targeting a unique C5 epitope, allowing for efficacy regardless of the R885H SNP. This study highlights crovalimab's distinctive molecular features, showing its eliminated binding to Fcγ receptors and C1q, alongside its optimized antigen binding characteristics. The impact of charge engineering was reconfirmed in mice, demonstrating faster C5 clearance than recycling antibodies. Notably, in the maintenance dosing regimen, crovalimab neutralizes approximately seven C5 molecules per antibody on average. Furthermore, its design also reduces the viscosity to facilitate high-concentration formulations suitable for subcutaneous delivery. Consequently, crovalimab offers a four-weekly subcutaneous injection regimen for PNH, marking a substantial improvement in treatment convenience and potentially transforming patients' quality of life. [ABSTRACT FROM AUTHOR]

Published
2024
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4. A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a nonhemophilic state

Author

Teranishi-Ikawa, Yuri, primary, Soeda, Tetsuhiro, additional, Koga, Hikaru, additional, Yamaguchi, Kazuki, additional, Kato, Kazuki, additional, Esaki, Keiko, additional, Asanuma, Kentaro, additional, Funaki, Miho, additional, Ichiki, Mina, additional, Ikuta, Yuri, additional, Ito, Shunsuke, additional, Joyashiki, Eri, additional, Komatsu, Shun-Ichiro, additional, Muto, Atsushi, additional, Nishimura, Kei, additional, Okuda, Momoko, additional, Sanada, Hisakazu, additional, Sato, Motohiko, additional, Shibahara, Norihito, additional, Wakabayashi, Tetsuya, additional, Yamaguchi, Koji, additional, Matsusaki, Akiko, additional, Sampei, Zenjiro, additional, Shiraiwa, Hirotake, additional, Konishi, Hiroko, additional, Kawabe, Yoshiki, additional, Hattori, Kunihiro, additional, Kitazawa, Takehisa, additional, and Igawa, Tomoyuki, additional

Published
2023
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5. 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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8. Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement

Author

Sampei, Zenjiro, primary, Koo, Christine Xing’er, additional, Teo, Frannie Jiuyi, additional, Toh, Ying Xiu, additional, Fukuzawa, Taku, additional, Gan, Siok Wan, additional, Nambu, Takeru, additional, Ho, Adrian, additional, Honda, Kiyofumi, additional, Igawa, Tomoyuki, additional, Ahmed, Fariyal, additional, Wang, Cheng-I, additional, Fink, Katja, additional, and Nezu, Junichi, additional

Published
2023
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9. A bispecific antibody NXT007 exerts a hemostatic activity in hemophilia A monkeys enough to keep a non-hemophiliac state

Author

Teranishi-Ikawa, Yuri, primary, Soeda, Tetsuhiro, additional, Koga, Hikaru, additional, Yamaguchi, Kazuki, additional, Kato, Kazuki, additional, Esaki, Keiko, additional, Asanuma, Kentaro, additional, Funaki, Miho, additional, Ichiki, Mina, additional, Ikuta, Yuri, additional, Ito, Shunsuke, additional, Joyashiki, Eri, additional, Komatsu, Shun-Ichiro, additional, Muto, Atsushi, additional, Nishimura, Kei, additional, Okuda, Momoko, additional, Sanada, Hisakazu, additional, Sato, Motohiko, additional, Shibahara, Norihito, additional, Wakabayashi, Tetsuya, additional, Yamaguchi, Koji, additional, Matsusaki, Akiko, additional, Sampei, Zenjiro, additional, Shiraiwa, Hirotake, additional, Konishi, Hiroko, additional, Kawabe, Yoshiki, additional, Hattori, Kunihiro, additional, Kitazawa, Takehisa, additional, and Igawa, Tomoyuki, additional

Published
2022
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11. Elimination of plasma soluble antigen in cynomolgus monkeys by combining pH-dependent antigen binding and novel Fc engineering

Author

Hori, Yuji, primary, Ohmine, Ken, additional, Katada, Hitoshi, additional, Noguchi, Yuki, additional, Sato, Kazuki, additional, Nambu, Takeru, additional, Adeline, Lam Runyi, additional, Wan, Gan Siok, additional, Haraya, Kenta, additional, Ozeki, Kazuhisa, additional, Nanami, Masahiko, additional, Tachibana, Tatsuhiko, additional, Sampei, Zenjiro, additional, Kuramochi, Taichi, additional, Nezu, Junichi, additional, Hattori, Kunihiro, additional, and Igawa, Tomoyuki, additional

Published
2022
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12. 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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13. Efficient production of bispecific antibody by FAST-IgTM and its application to NXT007 for the treatment of hemophilia A.

Author

Koga, Hikaru, Yamano, Takashi, Betancur, Juan, Nagatomo, Satoko, Ikeda, Yousuke, Yamaguchi, Kazuki, Nabuchi, Yoshiaki, Sato, Kazuki, Teranishi-Ikawa, Yuri, Sato, Motohiko, Hirayama, Hiroyuki, Hayasaka, Akira, Torizawa, Takuya, Haraya, Kenta, Sampei, Zenjiro, Shiraiwa, Hirotake, Kitazawa, Takehisa, Igawa, Tomoyuki, and Kuramochi, Taichi

Published
2023
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14. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model

Author

Kitazawa, Takehisa, Igawa, Tomoyuki, Sampei, Zenjiro, Muto, Atsushi, Kojima, Tetsuo, Soeda, Tetsuhiro, Yoshihashi, Kazutaka, Okuyama-Nishida, Yukiko, Saito, Hiroyuki, Tsunoda, Hiroyuki, Suzuki, Tsukasa, Adachi, Hideki, Miyazaki, Taro, Ishii, Shinya, Kamata-Sakurai, Mika, Iida, Takeo, Harada, Aya, Esaki, Keiko, Funaki, Miho, Moriyama, Chifumi, Tanaka, Eriko, Kikuchi, Yasufumi, Wakabayashi, Tetsuya, Wada, Manabu, Goto, Masaaki, Toyoda, Takeshi, Ueyama, Atsunori, Suzuki, Sachiyo, Haraya, Kenta, Tachibana, Tatsuhiko, Kawabe, Yoshiki, Shima, Midori, Yoshioka, Akira, and Hattori, Kunihiro

Subjects
Diagnosis, Drug therapy, Physiological aspects, Research, Causes of, Blood coagulation factors -- Physiological aspects -- Research, Hemophilia -- Causes of -- Diagnosis -- Drug therapy -- Research, Antibodies -- Physiological aspects -- Research, Factor VIII -- Physiological aspects -- Research, Viral antibodies -- Physiological aspects -- Research, Blood coagulation factor VIII -- Physiological aspects -- Research
Abstract

About 1 in 10,000 males suffer from hemophilia A (6). Approximately half of all patients with hemophilia A are classified as having severe disease (7), defined as Despite these advantages, [...], Hemophilia A is a bleeding disorder resulting from coagulation factor VIII (FVIII) deficiency. Exogenously provided FVIII effectively reduces bleeding complications in patients with severe hemophilia A. In approximately 30% of such patients, however, the 'foreignness' of the FVIII molecule causes them to develop inhibitory antibodies against FVIII (inhibitors), precluding FVIII treatment in this set of patients (1-3). Moreover, the poor pharmacokinetics of FVIII, attributed to low subcutaneous bioavailability and a short half-life of 0.5 d, necessitates frequent intravenous injections (3-5). To overcome these drawbacks, we generated a humanized bispecific antibody to factor IXa (FIXa) and factor X (FX), termed hBS23, that places these two factors into spatially appropriate positions and mimics the cofactor function of FVIII. hBS23 exerted coagulation activity in FVIII-deficient plasma, even in the presence of inhibitors, and showed in vivo hemostatic activity in a nonhuman primate model of acquired hemophilia A. Notably, hBS23 had high subcutaneous bioavailability and a 2-week half-life and would not be expected to elicit the development of FVIII-specific inhibitory antibodies, as its molecular structure, and hence antigenicity, differs from that of FVIII. A long-acting, subcutaneously injectable agent that is unaffected by the presence of inhibitors could markedly reduce the burden of care for the treatment of hemophilia A.

Published
2012
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17. Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody

Author

Sampei, Zenjiro, primary, Haraya, Kenta, additional, Tachibana, Tatsuhiko, additional, Fukuzawa, Taku, additional, Shida-Kawazoe, Meiri, additional, Gan, Siok Wan, additional, Shimizu, Yuichiro, additional, Ruike, Yoshinao, additional, Feng, Shu, additional, Kuramochi, Taichi, additional, Muraoka, Masaru, additional, Kitazawa, Takehisa, additional, Kawabe, Yoshiki, additional, Igawa, Tomoyuki, additional, Hattori, Kunihiro, additional, and Nezu, Junichi, additional

Published
2018
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19. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases

Author

Fukuzawa, Taku, primary, Sampei, Zenjiro, additional, Haraya, Kenta, additional, Ruike, Yoshinao, additional, Shida-Kawazoe, Meiri, additional, Shimizu, Yuichiro, additional, Gan, Siok Wan, additional, Irie, Machiko, additional, Tsuboi, Yoshinori, additional, Tai, Hitoshi, additional, Sakiyama, Tetsushi, additional, Sakamoto, Akihisa, additional, Ishii, Shinya, additional, Maeda, Atsuhiko, additional, Iwayanagi, Yuki, additional, Shibahara, Norihito, additional, Shibuya, Mitsuko, additional, Nakamura, Genki, additional, Nambu, Takeru, additional, Hayasaka, Akira, additional, Mimoto, Futa, additional, Okura, Yuu, additional, Hori, Yuji, additional, Habu, Kiyoshi, additional, Wada, Manabu, additional, Miura, Takaaki, additional, Tachibana, Tatsuhiko, additional, Honda, Kiyofumi, additional, Tsunoda, Hiroyuki, additional, Kitazawa, Takehisa, additional, Kawabe, Yoshiki, additional, Igawa, Tomoyuki, additional, Hattori, Kunihiro, additional, and Nezu, Junichi, additional

Published
2017
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21. 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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22. Efficient production of bispecific antibody by FAST-IgTMand its application to NXT007 for the treatment of hemophilia A

Author

Koga, Hikaru, Yamano, Takashi, Betancur, Juan, Nagatomo, Satoko, Ikeda, Yousuke, Yamaguchi, Kazuki, Nabuchi, Yoshiaki, Sato, Kazuki, Teranishi-Ikawa, Yuri, Sato, Motohiko, Hirayama, Hiroyuki, Hayasaka, Akira, Torizawa, Takuya, Haraya, Kenta, Sampei, Zenjiro, Shiraiwa, Hirotake, Kitazawa, Takehisa, Igawa, Tomoyuki, and Kuramochi, Taichi

Abstract

ABSTRACTEfficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology – Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.

Published
2023
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24. Identification and Multidimensional Optimization of an Asymmetric Bispecific IgG Antibody Mimicking the Function of Factor VIII Cofactor Activity

Author

Sampei, Zenjiro, primary, Igawa, Tomoyuki, additional, Soeda, Tetsuhiro, additional, Okuyama-Nishida, Yukiko, additional, Moriyama, Chifumi, additional, Wakabayashi, Tetsuya, additional, Tanaka, Eriko, additional, Muto, Atsushi, additional, Kojima, Tetsuo, additional, Kitazawa, Takehisa, additional, Yoshihashi, Kazutaka, additional, Harada, Aya, additional, Funaki, Miho, additional, Haraya, Kenta, additional, Tachibana, Tatsuhiko, additional, Suzuki, Sachiyo, additional, Esaki, Keiko, additional, Nabuchi, Yoshiaki, additional, and Hattori, Kunihiro, additional

Published
2013
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25. Hemostatic Effect of a Novel Bispecific Antibody (ACE910) Against Activated Factor IX and Factor X in an Acquired Hemophilia A Model

Author

Muto, Atsushi, primary, Kitazawa, Takehisa, additional, Yoshihasi, Kazutaka, additional, Takeda, Minako, additional, Soeda, Tetsuhiro, additional, Igawa, Tomoyuki, additional, Sampei, Zenjiro, additional, Sakamoto, Yuichiro, additional, Okuyama-Nishida, Yukiko, additional, Saito, Hiroyuki, additional, Kawabe, Yoshiki, additional, Shima, Midori, additional, Yoshioka, Akira, additional, and Hattori, Kunihiro, additional

Published
2012
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26. Generation of a Novel Bispecific Antibody (ACE910) Against Activated Factor IX and Factor X Mimicking the Function of Factor VIII Cofactor Activity

Author

Igawa, Tomoyuki, primary, Sampei, Zenjiro, additional, Soeda, Tetsuhiro, additional, Okuyama-Nishida, Yukiko, additional, Moriyama, Chifumi, additional, Wakabayashi, Tetsuya, additional, Tanaka, Eriko, additional, Muto, Atsushi, additional, Kojima, Tetsuo, additional, Kitazawa, Takehisa, additional, Yoshihashi, Kazutaka, additional, Harada, Aya, additional, Funaki, Miho, additional, Haraya, Kenta, additional, Tatsuhiko, Tachibana, additional, Suzuki, Sachiyo, additional, Esaki, Keiko, additional, Nabuchi, Yoshiaki, additional, and Hattori, Kunihiro, additional

Published
2012
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27. Gene cloning and deletion analysis of chitinase J from alkaliphilic Bacillus sp. strain J813

Author

Sampei, Zenjiro, Nagao, Yuri, Fukazawa, Tetsuya, Fukagawa, Satoko, Matsuo, Takatoshi, Endo, Kimiko, Yatsunami, Rie, and Nakamura, Satoshi

Abstract

Alkaliphilic <it>Bacillus</it> sp. strain J813 produces a novel chitinase (chitinase J). The gene encoding chitinase J (<it>chij</it>) was cloned and sequenced. Deduced amino acid sequence revealed that Chij contained a family 18 catalytic domain, a fibronectin type Ill-like domain and a chitinbinding domain. Analysis of deletion derivatives indicated that the chitin-binding domain was important for binding to chitin and it enhanced the hydrolysis of insoluble chitin. The subsites existing in the catalytic domain of Chij was thought to bind to insoluble chitosan, although Chij did not hydrolyze chitosan. Some amino acid-substituted mutants were prepared and characterized, suggesting that Glul98 should be the catalytic residue of Chij.

Published
2004
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28. Efficient production of bispecific antibody by FAST-Ig TM and its application to NXT007 for the treatment of hemophilia A.

Author

Koga H, Yamano T, Betancur J, Nagatomo S, Ikeda Y, Yamaguchi K, Nabuchi Y, Sato K, Teranishi-Ikawa Y, Sato M, Hirayama H, Hayasaka A, Torizawa T, Haraya K, Sampei Z, Shiraiwa H, Kitazawa T, Igawa T, and Kuramochi T

Subjects
Animals, Protein Engineering methods, Cell Line, Dimerization, Mammals, Antibodies, Bispecific, Hemophilia A
Abstract

Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.

Published
2023
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29. 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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