Review
Immunology
Jingyue Kang, Tonglin Sun, Yan Zhang
Summary: Bispecific antibodies (bsAbs) are artificial antibodies that can bind to different antigens or different epitopes on the same antigen, thanks to their two distinct antigen-binding sites. They have shown significant potential in tumor treatment and have been extensively researched. Currently, 7 bsAbs have been approved for marketing worldwide, with over 200 bsAbs in various stages of clinical and preclinical research.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Chang-ling Gu, Hai-xia Zhu, Lan Deng, Xiao-qing Meng, Kai Li, Wei Xu, Le Zhao, Yue-qin Liu, Zhen-ping Zhu, Hao-min Huang
Summary: The study developed a bispecific antibody targeting PD1 and HER2, showing high affinities and potent antitumor activities in vitro and in vivo. The BsAb also demonstrated both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells through antibody-dependent cellular cytotoxicity.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Hua-ying Li, Yi-li Chen, Xiang-nan Deng, Huan-huan Li, Jie Tan, Guo-jian Liu, Yu-juan Zheng, Min Pei, Kai-ting Peng, Li-li Yue, Xiao-jia Chen, Yu Liu, Yong-shan Zhao, Chun-he Wang
Summary: The clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is limited due to low response rates and drug resistance. Combining PD-1/PD-L1 and B7-H3 pathways may provide additional therapeutic benefits. In this study, a stable B7-H3xPD-L1 bispecific antibody (BsAb) was generated and showed enhanced antitumor activities in a tumor model. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Jie Chen, Zhidi Pan, Lei Han, Yuexian Zhou, Huifang Zong, Lei Wang, Rui Sun, Hua Jiang, Yueqing Xie, Yunsheng Yuan, Mingyuan Wu, Yanling Bian, Baohong Zhang, Jianwei Zhu
Summary: The study constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3, showing high affinity and anti-tumor activity against gastric cancer in vitro and in vivo. It demonstrated stronger T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity compared to the parent monoclonal antibody, indicating potential therapeutic efficacy for gastric cancer.
Article
Oncology
Zhaoming Wang, Chaobo Yin, Lawrence G. Lum, Andrean Simons, George J. Weiner
Summary: Research suggests that treatment with anti-CD3 x anti-cancer bispecific antibodies (bsAbs) may enhance T cell help, maintaining long-term NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC).
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Immunology
Emilia Rabia, Veronique Garambois, Christine Dhommee, Christel Larbouret, Laurie Lajoie, Yoan Buscail, Gabriel Jimenez-Dominguez, Sylvie Choblet-Thery, Emmanuelle Liaudet-Coopman, Martine Cerutti, Marta Jarlier, Patrice Ravel, Laurent Gros, Nelly Pirot, Gilles Thibault, Eugene A. A. Zhukovsky, Pierre-Emmanuel Gerard, Andre Pelegrin, Jacques Colinge, Thierry Chardes
Summary: Using the BiXAb(TM) tetravalent platform, we generated bispecific antibodies against EGFR, HER2, or HER3 and compared them with single antibodies and antibody pair combinations. We selected 3Patri-1Cetu-Fc, 3Patri-1Matu-Fc, and 3Patri-2Trastu-Fc as lead candidates and tested their efficacy in mouse models of pancreatic cancer. This semi-rational/semi-empirical approach represents the first attempt to identify potent bispecific antibodies against ErbB family members in pancreatic cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Juan Tang, Youling Gong, Xuelei Ma
Summary: The discovery of oncogenes and immune checkpoints has revolutionized the treatment of melanoma in the past 10 years. However, the current PD-L1 checkpoints lack specificity for tumors and target normal cells expressing PD-L1, thus reducing the efficacy on malignant melanoma and increasing the side effects. In addition, the treatment options for primary or secondary drug-resistant melanoma are limited. Bispecific antibodies bind tumor cells and immune cells by simultaneously targeting two antigens, enhancing the anti-tumor targeting effect and cytotoxicity and reducing drug-resistance in malignant melanoma, thus representing an emerging strategy to improve the clinical efficacy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Nami Tateyama, Hiroyuki Suzuki, Tomokazu Ohishi, Teizo Asano, Tomohiro Tanaka, Takuya Mizuno, Takeo Yoshikawa, Manabu Kawada, Mika K. Kaneko, Yukinari Kato
Summary: The bispecific antibody E134Bf-H77scFv exhibited antitumor activities against dEGFR/dHER2-positive canine tumors, suggesting its potential as a valuable treatment regimen.
Article
Oncology
Daisuke Kamakura, Ryutaro Asano, Hiroki Kawai, Masahiro Yasunaga
Summary: T cell-dependent bispecific antibody (TDB) induces T cell activation to eliminate tumor cells independently of MHC engagement, and may be a breakthrough immunotherapy for refractory cancer. The mechanism involves T cell-tumor cell contact for direct killing and cytokine secretion for contact-independent damage. TDB hEx3 shows promise against refractory CRC, targeting specific mutations and utilizing four action steps for tumor cell killing.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Physics, Fluids & Plasmas
Enggar Alfianto, Kazumasa Ikuse, Satoshi Hamaguchi
Summary: When a phosphate-buffered saline (PBS) solution is exposed to atmospheric-pressure plasmas generated in air, hydrogen peroxide (H2O2) in the solution is decomposed by hypochlorite (OCl-), formed from reactions between chlorine ions (Cl-) in the PBS solution and plasma-generated reactive oxygen species. Liquid-phase chemical reactions were simulated to identify the reaction mechanisms, revealing that H2O2 decomposes mainly due to the presence of OCl-. However, in the presence of abundant hydroxyl (OH) radicals, a more efficient H2O2 decomposition pathway can occur through a chlorine monoxide cycle, where OCl- reacts with OH to form chlorine monoxide (ClO) which then decomposes HOCl, rather than direct OCl- decomposition of H2O2.
PLASMA SOURCES SCIENCE & TECHNOLOGY
(2023)
Article
Oncology
Nishant Mohan, Xiao Luo, Yi Shen, Zachary Olson, Atul Agrawal, Yukinori Endo, David S. Rotstein, Lorraine C. Pelosof, Wen Jin Wu
Summary: TNBC, accounting for 10-20% of diagnosed breast cancers with poor prognosis, urgently requires novel targeted therapies. A bispecific antibody targeting EGFR and VEGFR2 demonstrated comprehensive anti-tumor activity by inhibiting multiple mechanisms, showing potential as a targeted therapy for TNBC.
Review
Chemistry, Medicinal
Daisuke Kamakura, Ryutaro Asano, Masahiro Yasunaga
Summary: T-BsAbs are a promising immunotherapy for various cancers, capable of activating T cells and inducing tumor cell death by dual-binding tumor antigens and CD3 subunits. Unlike immune checkpoint inhibitors, T-BsAbs serve as accelerators of T cells by redirecting host immunity towards tumors through CD3 engagement.
Article
Oncology
Mehdi Mohammadi, Mahmood Jeddi-Tehrani, Forough Golsaz-Shirazi, Mohammad Arjmand, Fatemeh Torkashvand, Tannaz Bahadori, Mohammad Ali Judaki, Fariba Shiravi, Hengameh Ahmadi Zare, Farzaneh Notash Haghighat, Maryam Mobini, Fazel Shokri, Mohammad Mehdi Amiri
Summary: HER2 overexpression is common in cancer, but targeted therapy with anti-HER2 monoclonal antibodies (mAbs) does not benefit all patients. Fc engineering is a common approach to improve the efficacy of mAbs. We have developed an anti-HER2 bispecific mAb, BiHT, which showed promising antitumor activity. To improve its therapeutic efficacy, we aimed to modify the Fc of BiHT.
JOURNAL OF IMMUNOTHERAPY
(2023)
Article
Optics
Bernhard Lau, Dietmar Becher, Martin Hessling
Summary: Visible light with a wavelength of about 405 nm has been proven to have an antiviral effect on coronaviruses, with significant virus reduction observed within half an hour. The study suggests that ultraviolet radiation is suitable for reducing coronaviruses.
Article
Immunology
Francoise Gondois-Rey, Thomas Miller, Vladimir Laletin, Xavier Morelli, Yves Collette, Jacques Nunes, Daniel Olive
Summary: Immunotherapies targeting the CD47-SIRPα immune checkpoint have promising clinical potential but are limited by toxicities associated with non-tumor cell destruction. This study found that anti-CD47 antibodies can kill T cells through a combination of trogocytosis and respiratory burst induced by ADCC and CD47-SIRPα checkpoint blockade. The results also suggest that SIRPα tightly controls activation of NADPH oxidase, which is important for immature PMNs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Mingyan Cao, Sri Hari Raju Mulagapati, Bhargavi Vemulapalli, Jihong Wang, Sergei V. Saveliev, Marjeta Urh, Alan Hunter, Dengfeng Liu
ANALYTICAL BIOCHEMISTRY
(2019)
Article
Biotechnology & Applied Microbiology
Nitin Agarwal, Alison Mason, Rahul Pradhan, Jan Kemper, Allen Bosley, Dimitra Serfiotis-Mitsa, Jihong Wang, Viv Lindo, Sanjeev Ahuja, Diane Hatton, James Savery, Guillermo Miro-Quesada
BIOTECHNOLOGY PROGRESS
(2019)
Article
Chemistry, Medicinal
Mingyan Cao, Weichen Xu, Ben Niu, Ivy Kabundi, Haibin Luo, Meagan Prophet, Weimin Chen, Dengfeng Liu, Sergei Saveliev, Marjeta Urh, Jihong Wang
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Medicine, Research & Experimental
Gargi Roy, Jason Reier, Andrew Garcia, Tom Martin, Megan Rice, Jihong Wang, Meagan Prophet, Ronald Christie, William Dall'Acqua, Sanjeev Ahuja, Michael A. Bowen, Marcello Marelli
Article
Biotechnology & Applied Microbiology
Michael W. Handlogten, Jihong Wang, Sanjeev Ahuja
BIOTECHNOLOGY AND BIOENGINEERING
(2020)
Article
Medicine, Research & Experimental
Jun Kim, Yoen Joo Kim, Mingyan Cao, Niluka De Mel, Kenneth Miller, Jared S. Bee, Jihong Wang, Xiangyang Wang, Methal Albarghouthi
Article
Multidisciplinary Sciences
Xiaojun Lu, Lee Ann Machiesky, Niluka De Mel, Qun Du, Weichen Xu, Michael Washabaugh, Xu-Rong Jiang, Jihong Wang
SCIENTIFIC REPORTS
(2020)
Article
Chemistry, Medicinal
Xiaojun Lu, Shihua Lin, Niluka De Mel, Arun Parupudi, Jared Delmar, Madhu Pandey, Xiangyang Wang, Jihong Wang
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Multidisciplinary Sciences
Ben Niu, Michael Martinelli II, Yang Jiao, Chunlei Wang, Mingyan Cao, Jihong Wang, Eric Meinke
Article
Biochemical Research Methods
Trina Mouchahoir, John E. Schiel, Rich Rogers, Alan Heckert, Benjamin J. Place, Aaron Ammerman, Xiaoxiao Li, Tom Robinson, Brian Schmidt, Chris M. Chumsae, Xinbi Li, Anton Manuilov, Bo Yan, Gregory O. Staples, Da Ren, Alexander J. Veach, Dongdong Wang, Wael Yared, Zoran Sosic, Yan Wang, Li Zang, Anthony M. Leone, Peiran Liu, Richard Ludwig, Li Tao, Wei Wu, Ahmet Cansizoglu, Andrew Hanneman, Greg W. Adams, Irina Perdivara, Hunter Walker, Margo Wilson, Arnd Brandenburg, Nick DeGraan-Weber, Stefano Gotta, Joe Shambaugh, Melissa Alvarez, X. Christopher Yu, Li Cao, Chun Shao, Andrew Mahan, Hirsh Nanda, Kristen Nields, Nancy Nightlinger, Helena Maria Barysz, Michael Jahn, Ben Niu, Jihong Wang, Gabriella Leo, Nunzio Sepe, Yan-Hui Liu, Bhumit A. Patel, Douglas Richardson, Yi Wang, Daniela Tizabi, Oleg Borisov, Yali Lu, Ernest L. Maynard, Albrecht Gruhler, Kim F. Haselmann, Thomas N. Krogh, Carsten P. Sonksen, Simon Letarte, Sean Shen, Kristin Boggio, Keith Johnson, Wenqin Ni, Himakshi Patel, David Ripley, Jason C. Rouse, Ying Zhang, Carly Daniels, Andrew Dawdy, Olga Friese, Thomas W. Powers, Justin B. Sperry, Josh Woods, Eric Carlson, K. Ilker Sen, St John Skilton, Michelle Busch, Anders Lund, Martha Stapels, Xu Guo, Sibylle Heidelberger, Harini Kaluarachchi, Sean McCarthy, John Kim, Jing Zhen, Ying Zhou, Sarah Rogstad, Xiaoshi Wang, Jing Fang, Weibin Chen, Ying Qing Yu, John G. Hoogerheide, Rebecca Scott, Hua Yuan
Summary: The MAM Consortium conducted an interlaboratory study to evaluate NPD performance across the industry, with results showing representative high-resolution MS capabilities. Critical elements of NPD were identified to further refine the methodology and speed up adoption into manufacturer-specific protein therapeutic product life cycles.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Chen Qian, Ben Niu, Rod Brian Jimenez, Jihong Wang, Methal Albarghouthi
Summary: The multi-attribute method based on liquid chromatography-tandem mass spectrometry is a powerful tool for monitoring multiple product quality attributes simultaneously, and a need for a universal and high-throughput workflow has been identified to better implement this method. Manual sample preparation for MAM is labor intensive and produces variations, therefore a fully automated peptide mapping procedure has been developed to improve sample handling capacity and outcome reproducibility.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Chemistry, Medicinal
Mingyan Cao, Niluka De Mel, Jihong Wang, Conner Parthemore, Yang Jiao, Weimin Chen, Shihua Lin, Dengfeng Liu, Greg Kilby, Xiaoyu Chen
Summary: In this study, N-terminal E cyclization was identified as the major degradation pathway for monoclonal antibodies and bispecific antibodies in lyophilized formulations. The use of salt-gradient ion exchange chromatography and hydrophobic interaction chromatography effectively separated pE, and pE did not affect the binding activity of the antibodies. In vitro experiments suggested a potential role of serum matrix in pE conversion.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Jared A. Delmar, Eugen Buehler, Ashwin K. Chetty, Agastya Das, Guillermo Miro Quesada, Jihong Wang, Xiaoyu Chen
Summary: The study focuses on the photooxidation of Met and Trp residues in therapeutic proteins, creating computational models using machine learning algorithms, and identifying important parameters influencing photooxidation.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Chemistry, Medicinal
Jared A. Delmar, Claire Harris, Luigi Grassi, Nathaniel Macapagal, Jihong Wang, Diane Hatton, Weichen Xu
Summary: Mis-splicing events in the heavy chain transcript were found to generate LMW species, which were successfully removed by an optimized purification process. Transcriptomic analysis tools play a key role in identifying unknown species.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Medicine, Research & Experimental
Weimin Chen, Madhu Pandey, Hong Sun, Andrea Rolong, Mingyan Cao, Dengfeng Liu, Jihong Wang, Lingmin Zeng, Alan Hunter, Shihua Lin
Summary: T-cell-mediated immunotherapy has gained attention for targeting immune checkpoint molecules. Bispecific antibodies targeting two antigen targets have shown promise for cancer immunotherapy. Developing appropriate bioassays to measure potency and characterize biological properties of BsAbs is crucial. A dual target reporter bioassay presented here can accurately measure potency of BsAbs targeting CTLA-4 and PD-1, reflecting the potential MOA and synergistic effects of these bispecific biologics.