Review
Immunology
Chang Liu, Hong Lin, Limin Cao, Kaiqiang Wang, Jianxin Sui
Summary: This paper classified and summarized the unique antigen-binding mechanisms, different antigen binding cases, and current maturation strategies of single-domain antibodies (sdAbs), laying a theoretical foundation for further application of sdAbs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Gemma L. Gordon, Henriette L. Capel, Bora Guloglu, Eve Richardson, Ryan L. Stafford, Charlotte M. Deane
Summary: Antibodies and single-domain antibodies (sdAbs) differ in the structures of their binding sites, but sdAbs can target epitopes of equal size to antibodies despite their smaller paratopes. The paratopes of sdAbs contribute more interactions per residue, and conserved framework residues play a crucial role in achieving comparable affinity. The accessibility of sdAb epitopes is only slightly less than that of antibodies, possibly due to differences in the orientation and compaction of CDR-H3 loops.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jesper Bergwik, Amanda Kristiansson, Jorgen Larsson, Simon Ekstrom, Bo Akerstrom, Maria Allhorn
Summary: A1M can bind to heparin and HS, and can be purified from human plasma using heparin affinity chromatography and size exclusion chromatography. The binding strength is inversely proportional to salt concentration and directly proportional to the sulfation degree of heparin and HS.
Article
Virology
Shenghua Qu, Xiaoyan Wang, Lixin Yang, Runze Meng, Chonglun Feng, Baolin Yang, Jingjing Huang, Qiong Li, Jiaying Wang, Dabing Zhang
Summary: The study mapped the epitope recognized by MAb 12F11 using alanine substitutions combined with dissociation constant analysis, revealing one critical residue and 13 peripheral residues. The antigenic site was shown to span four loops and three fl-strands, contributing to the understanding of the antigenic structure of the TMUV envelope protein.
Article
Multidisciplinary Sciences
Suguru Tamura, Hajime Ishiguro, Tatsuya Suwabe, Takayuki Katagiri, Kaori Cho, Kyoko Fuse, Yasuhiko Shibasaki, Tadahisa Mikami, Takero Shindo, Hiroshi Kitagawa, Michihiro Igarashi, Hirohito Sone, Masayoshi Masuko, Takashi Ushiki
Summary: Reduction of chondroitin sulfate in donor blood cells may suppress the severity of acute graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Catarina Marques, Celso A. Reis, Romain R. Vives, Ana Magalhaes
Summary: Heparan Sulfate Proteoglycans (HSPGs) play important roles in orchestrating cellular events in physiology and pathology by modulating cell signaling networks and cell interactions. The structural features of HS chains are crucial for the functions of HSPGs, influencing protein interactions and signaling. The tightly controlled biosynthetic pathway of HS leads to structural diversity, which is differently regulated in various tissues, developmental stages, and pathologies such as cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Miaomiao Li, Lars C. Pedersen, Ding Xu
Summary: Heparan sulfate-binding proteins (HSBPs) are structurally diverse extracellular and membrane attached proteins that interact with HS under normal physiological conditions. Interactions with HS offer an additional level of control over the localization and function of HSBPs. Manipulating HS-protein interactions could be explored as a therapeutic strategy to selectively antagonize/activate HSBPs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Medicine, Research & Experimental
Meijie Tian, Adam T. Cheuk, Jun S. Wei, Abdalla Abdelmaksoud, Hsien-Chao Chou, David Milewski, Michael C. Kelly, Young K. Song, Christopher M. Dower, Nan Li, Haiying Qin, Yong Yean Kim, Jerry T. Wu, Xinyu Wen, Mehdi Benzaoui, Katherine E. Masih, Xiaolin Wu, Zhongmei Zhang, Sherif Badr, Naomi Taylor, Brad St. Croix, Mitchell Ho, Javed Khan
Summary: This study identified high-activity CARs against neuroblastoma using multiple approaches and demonstrated the potential of targeting multiple TAAs with BiCisCAR to overcome heterogenous expression in solid tumors. The multimodal approach integrating competitive expansion, P-COCC, and cytotoxicity assays proved to be effective in identifying potent CARs.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Chemistry, Applied
Friederike Eilts, Sarah Bauer, Keith Fraser, Jonathan S. Dordick, Michael W. Wolff, Robert J. Linhardt, Fuming Zhang
Summary: This review examines the current research on the involvement of heparan sulfate (HS) in SARS-CoV-2 infection, the implications of viral mutations, and the use of glycosaminoglycans (GAGs) and other sulfated polysaccharides as antiviral agents.
CARBOHYDRATE POLYMERS
(2023)
Article
Chemistry, Organic
Mihaly Herczeg, Fruzsina Demeter, Erika Lisztes, Mark Racsko, Balazs Istvan Toth, Istvan Timari, Zsuzsanna Bereczky, Katalin E. Kover, Aniko Borbas
Summary: L-Iduronic acid is a key component of heparin and heparan sulfate polysaccharides, playing a crucial role in their binding to proteins. However, its synthesis is challenging. In this study, we successfully synthesized a biologically active heparinoid oligosaccharide by replacing L-Iduronic acid with a different sugar unit. This is the first example of a biologically active heparinoid anticoagulant with a sugar unit other than L-Iduronic acid.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Immunology
Yan Fang, Pengcheng Sun, Xuping Xie, Mingjian Du, Fenghe Du, Jianfeng Ye, Birte K. Kalveram, Jessica A. Plante, Kenneth S. Plante, Bo Li, Xiao-chen Bai, Pei-Yong Shi, Zhijian J. Chen
Summary: The study utilized LIBRA-seq technology to identify an antibody, SW186, that exhibits broad neutralizing activity against various SARS-CoV-2 variants. The cryo-EM structure analysis revealed that SW186 targets a conserved epitope on the receptor binding domain of the viral spike protein. In mouse models, administration of SW186 significantly reduced viral loads in the lungs.
SCIENCE IMMUNOLOGY
(2022)
Article
Microbiology
Rong-Hong Hua, Shu-Jian Zhang, Bei Niu, Jin-Ying Ge, Ting Lan, Zhi-Gao Bu
Summary: A broad-spectrum neutralizing antibody and its highly conserved epitope in the receptor-binding domain (RBD) of SARS-CoV-2 have been identified in this study. The antibody can neutralize all known variants, and the epitope is conserved in all variants. This research provides new insights for developing broad-spectrum prophylactic vaccines and therapeutic antibodies.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Cheng Li, Wuqiang Zhan, Zhenlin Yang, Chao Tu, Gaowei Hu, Xiang Zhang, Wenping Song, Shujuan Du, Yuanfei Zhu, Keke Huang, Yu Kong, Meng Zhang, Qiyu Mao, Xiaodan Gu, Yi Zhang, Youhua Xie, Qiang Deng, Yuanlin Song, Zhenguo Chen, Lu Lu, Shibo Jiang, Yanling Wu, Lei Sun, Tianlei Ying
Summary: This study identifies two highly conserved regions on the Omicron variant receptor-binding domain that are recognized by broadly neutralizing antibodies, and generates a bispecific antibody that can simultaneously bind these regions, showing excellent therapeutic efficacy and neutralization breadth.
Article
Multidisciplinary Sciences
Dami A. Collier, Anna De Marco, Isabella A. T. M. Ferreira, Bo Meng, Rawlings P. Datir, Alexandra C. Walls, Steven A. Kemp, Jessica Bassi, Dora Pinto, Chiara Silacci-Fregni, Siro Bianchi, M. Alejandra Tortorici, John Bowen, Katja Culap, Stefano Jaconi, Elisabetta Cameroni, Gyorgy Snell, Matteo S. Pizzuto, Alessandra Franzetti Pellanda, Christian Garzoni, Agostino Riva, Anne Elmer, Nathalie Kingston, Barbara Graves, Laura E. Mccoy, Kenneth G. C. Smith, John R. Bradley, Nigel Temperton, Lourdes Ceron-Gutierrez, Gabriela Barcenas-Morales, William Harvey, Herbert W. Virgin, Antonio Lanzavecchia, Luca Piccoli, Rainer Doffinger, Mark Wills, David Veesler, Davide Corti, Ravindra K. Gupta
Summary: The B.1.1.7 variant of SARS-CoV-2 exhibited reduced neutralization by vaccines and antibodies from recovered COVID-19 patients, with a more substantial loss seen when introducing the E484K mutation. This mutation poses a threat to the efficacy of the BNT162b2 vaccine.
Review
Biochemistry & Molecular Biology
Yi-En Liao, Jian Liu, Katelyn Arnold
Summary: Heparan sulfates and heparan sulfate binding proteins play crucial roles in regulating vascular homeostasis and host response in sepsis. Dysregulation of these molecules can exacerbate inflammation and coagulation. Understanding the structure-function relationship between heparan sulfates and heparan sulfate binding proteins is essential for drug development and potential therapeutic interventions in sepsis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biology
Ramin Dubey, Peter van Kerkhof, Ingrid Jordens, Tomas Malinauskas, Ganesh Pusapati, Joseph K. Mckenna, Dan Li, Jan E. Carette, Mitchell Ho, Christian Siebold, Madelon Maurice, Andres M. Lebensohn, Rajat Rohatgi
Review
Cell Biology
Nan Li, Madeline R. Spetz, Mitchell Ho
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Panpan Meng, Yi-Fan Zhang, Wangli Zhang, Xin Chen, Tong Xu, Sheng Hu, Xinjun Liang, Mingqian Feng, Xiaoqing Yang, Mitchell Ho
Summary: The study revealed FAT1 as a novel interacting protein of GPC3, with both showing elevated expression in HCC cells, being up-regulated under hypoxia conditions, and regulating the expression of EMT-related genes to promote HCC cell migration.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Xue Yan Cui, Geir Erland Tjonnfjord, Sandip M. Kanse, Anders Erik Astrup Dahm, Nina Iversen, Christiane Filion Myklebust, Ling Sun, Zhong Xing Jiang, Thor Ueland, James J. Campbell, Mitchell Ho, Per Morten Sandset
Summary: Plasma TFPI levels are higher in CLL patients compared to healthy controls, especially in those with advanced disease. TFPI enhances CXCL12-mediated migration of CLL cells through increased expression of the CXCR7 receptor. TFPI, which co-localizes with GPC3, plays a crucial role in regulating CXCR7 expression and TEM.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Nan Li, Madeline R. Spetz, Dan Li, Mitchell Ho
Summary: Cancer immunotherapies have revolutionized the treatment of adult malignancies and are now being translated to pediatric oncology. Successful immunotherapeutic agents for pediatric cancers include chimeric antigen receptor T-cell therapy, bispecific antibodies targeting CD19, and anti-GD2 monoclonal antibody. Advancements in tumor immunology and genome profiling have led to the identification of new tumor-specific antigens, such as Glypican 2 (GPC2) and B7-H3 (CD276), which could have a positive impact on pediatric cancer treatment.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Luan Sun, Fang Gao, Zhanhui Gao, Lei Ao, Na Li, Sujuan Ma, Meng Jia, Nan Li, Peihua Lu, Beicheng Sun, Mitchell Ho, Shaochang Jia, Tong Ding, Wei Gao
Summary: This study constructed two types of CAR-T cells targeting different epitopes of GPC3 to investigate the influence of sGPC3 on the activation and cytotoxicity of CAR-T cells in vitro and in vivo. Results showed that sGPC3 significantly inhibited the release of cytokines and the cytotoxicity of anti-GPC3 CAR-T cells in vitro, and in mouse models sGPC3 expression in Hep3B xenograft tumors led to a worse response to CAR-T cell treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Cell Biology
Jiajia Pan, Mitchell Ho
Summary: Glypican-1 (GPC1) modulates various signaling pathways by interacting with pathway ligands and receptors, impacting the pathways' activation or inhibition based on specific GPC1 domain interactions with pathway components and cell surface context.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Oncology
Zhijian Duan, Mitchell Ho
Summary: Antibody-based immunotherapies have shown efficacy in cancer treatment, but their targets are limited. Research has shown that short peptides from intracellular targets could be potential immunotherapy targets. TCRm antibodies are a promising new direction, and future clinical studies will help further understand their mechanisms of action.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Xin Chen, Yanmin Chen, Rong Liang, Lanxin Xiang, Jingwen Li, Yuankui Zhu, Huixia He, Le Huang, Dianbao Zuo, Weihang Li, Xinjun Liang, Shuang Dong, Sheng Hu, Mitchell Ho, Mingqian Feng
Summary: This study investigated the efficacy of six GPC3-targeted bispecific antibodies for the treatment of HCC, and found that the hYP7-OKT3-hFc antibody was the most effective. Combination with the chemotherapeutic drug Irinotecan further enhanced the therapeutic effect.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Dan Li, Hejiao English, Jessica Hong, Tianyuzhou Liang, Glenn Merlino, Chi-Ping Day, Mitchell Ho
Summary: CAR-T cell therapy has shown great potential in treating hematological malignancies, but its efficacy in solid tumors is limited. In this study, the researchers developed a CAR-T therapy targeting PD-L1 and successfully treated breast cancer and liver cancer, while also inhibiting tumor metastasis.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Oncology
Jiajia Pan, Nan Li, Alex Renn, Hu Zhu, Lu Chen, Min Shen, Matthew D. Hall, Min Qian, Ira Pastan, Mitchell Ho
Summary: The cell surface proteoglycan GPC1 is overexpressed in multiple types of human cancers, including pancreatic cancer. In this study, researchers constructed GPC1-targeted immunotoxins and found that these immunotoxins can inhibit pancreatic tumor growth. Combining the immunotoxin with irinotecan further enhanced its efficacy.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
Jessica Hong, Hyung Joon Kwon, Raul Cachau, Catherine Z. Chen, Kevin John Butay, Zhijian Duan, Dan Li, Hua Ren, Tianyuzhou Liang, Jianghai Zhu, Venkata P. Dandey, Negin P. Martin, Dominic Esposito, Uriel Ortega-Rodriguez, Miao Xu, Mario J. Borgnia, Hang Xie, Mitchell Ho
Summary: The study constructed large dromedary camel VHH phage libraries and successfully isolated two high-affinity nanobodies that showed broad neutralization activity against SARS-CoV-2 and its variants. These nanobodies can be used for therapeutic purposes against COVID-19 variants, and the dromedary camel VHH phage libraries serve as a unique platform for rapidly isolating potent nanobodies against future emerging viruses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Xiufen Liu, Masanori Onda, Nathan Watson, Raffit Hassan, Mitchell Ho, Tapan K. Bera, Junxia Wei, Anirban Chakraborty, Richard Beers, Qi Zhou, Asif Shajahan, Parastoo Azadi, Jingyu Zhan, Di Xia, Ira Pastan
Summary: Researchers have identified a monoclonal antibody that inhibits the shedding of the protein MSLN, which is highly expressed by cancer cells. The antibody binds to the protease-sensitive region of MSLN and CAR T cells produced with this antibody show superior antitumor activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Nan Li, Rosa Nguyen, Carol J. Thiele, Mitchell Ho
Summary: This study presents neuroblastoma metastatic and orthotopic mouse models to aid in the translation of CAR T cell therapy research. Additionally, we have established an analysis pipeline for evaluating the efficacy and immunological characteristics of CAR T cells and tumor cells.
Article
Cell Biology
Nan Li, Madeline B. Torres, Madeline R. Spetz, Ruixue Wang, Luyi Peng, Meijie Tian, Christopher M. Dower, Rosa Nguyen, Ming Sun, Chin-Hsien Tai, Natalia de Val, Raul Cachau, Xiaolin Wu, Stephen M. Hewitt, Rosandra N. Kaplan, Javed Khan, Brad St Croix, Carol J. Thiele, Mitchell Ho
Summary: The study utilized RNA sequencing analysis to identify high expression of GPC2 exons 3 and exons 7-10 in cancer but minimal expression in normal tissues. A monoclonal antibody CT3 was discovered and used to design CAR T cells for treating neuroblastoma. Genomic sequencing of T cells recovered from mice revealed potential CAR integration sites contributing to CART cell proliferation and persistence.
CELL REPORTS MEDICINE
(2021)