Review
Immunology
Lois Coenon, Martin Villalba
Summary: This review provides an overview of the latest strategies employed to improve antibody-dependent NK cell cytotoxicity, by enhancing the biological function of CD16a receptor.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Kate J. Dixon, Jianming Wu, Bruce Walcheck
Summary: Human natural killer (NK) cells target tumor antigens through interaction with IgG Fc receptors, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) against cancer cells. Engineering monoclonal antibodies and Fc receptors can enhance NK cell-mediated ADCC for cancer treatment. Targeting tumor antigens by modifying the Fc portion of antibodies or the FcR on NK cells is a key focus of research in improving mAb therapy efficacy.
Article
Immunology
Ran Salomon, Rony Dahan
Summary: The clinical use of anti-CD40 agonist monoclonal antibodies faces challenges due to dose-limiting toxicity. Novel approaches are being explored to overcome the systemic toxicity associated with CD40 agonism.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Stephen J. Blake, Jane James, Feargal J. Ryan, Jose Caparros-Martin, Georgina L. Eden, Yee C. Tee, John R. Salamon, Saoirse C. Benson, Damon J. Tumes, Anastasia Sribnaia, Natalie E. Stevens, John W. Finnie, Hiroki Kobayashi, Deborah L. White, Steve L. Wesselingh, Fergal O'Gara, Miriam A. Lynn, David J. Lynn
Summary: Immune agonist antibodies (IAAs) show promise as immunotherapies targeting co-stimulatory receptors, but their clinical translation is hindered by immune-mediated toxicities. Research shows that the gut microbiota plays a role in the toxicity induced by IAAs, with germ-free or antibiotic-treated mice experiencing reduced toxicities compared to conventional mice. MyD88 signaling is crucial for the immune response induced by IAAs, with antibiotic treatment not impairing the efficacy of IAAs in anti-tumor activity.
CELL REPORTS MEDICINE
(2021)
Article
Oncology
Hyeree Choi, Michelle Ho, Opeyemi S. Adeniji, Leila Giron, Devivasha Bordoloi, Abhijeet J. Kulkarni, Alfredo Perales Puchalt, Mohamed Abdel-Mohsen, Kar Muthumani
Summary: A panel of human anti-Siglec-9 hybridoma clones with high specificity and functionality were developed through immunizing mice with Siglec-9-encoding DNA and protein. The lead antibodies were found to enhance anti-tumor immune activity in vitro and significantly reduce tumor volume in an ovarian cancer humanized mouse model. These novel antibodies interfere with Siglec-9-mediated immunosuppression to augment anti-tumor immunity.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Vanessa Arato, Maria Michelina Raso, Gianmarco Gasperini, Francesco Berlanda Scorza, Francesca Micoli
Summary: Klebsiella pneumoniae is an opportunistic pathogen that has recently seen an increase in hypervirulent strains and multi-drug resistant clones. It has been prioritized as a critical antimicrobial resistance threat by the World Health Organization, leading to renewed interest in vaccine development and alternative treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Christina Claus, Claudia Ferrara-Koller, Christian Klein
Summary: The clinical development of 4-1BB agonists for cancer immunotherapy has generated significant interest, but the first generation of agonistic antibodies failed due to toxicity or lack of efficacy. Second-generation 4-1BB agonists addressing the limitations of the first generation are now being developed and entering clinical studies. This review provides an overview of the differences between these agonists and the challenges in their clinical development.
Review
Oncology
Alessio Ugolini, Marianna Nuti
Summary: The CD137 receptor, expressed by activated antigen-specific T-cells, plays a crucial role in driving immune responses against cancer. CD137(+) T-cells, capable of recognizing a wide range of tumor-derived peptides, have shown efficacy in killing cancer cells both in vitro and in vivo, making them a promising candidate for immunotherapy strategies. CD137-targeting monoclonal antibodies have demonstrated antitumor efficacy in cancer patients, with ongoing clinical trials to explore their potential in combination approaches of immunotherapy. Additionally, the intracellular domain of the CD137 receptor has been incorporated into anti-CD19 CAR-T cells approved for treating pediatric B-cell leukemia and refractory B-cell lymphoma.
Article
Immunology
Zuzana Antosova, Nada Podzimkova, Jakub Tomala, Katerina Augustynkova, Katerina Sajnerova, Eva Nedvedova, Milada Sirova, Guy de Martynoff, David Bechard, Ulrich Moebius, Marek Kovar, Radek Spisek, Irena Adkins
Summary: SOT101, a potential clinical candidate for cancer treatment, activates NK cells and CD8(+) T cells and enhances their cytotoxicity against tumor cells. When used in combination with approved monoclonal antibodies, it increases the killing of tumor cells. In an animal model, the combination of SOT101 and Daratumumab showed the strongest anti-tumor effect, supporting further investigation of this combination in clinical studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Mika Kamata-Sakurai, Yoshinori Narita, Yuji Hori, Takayuki Nemoto, Ryo Uchikawa, Masaki Honda, Naoka Hironiwa, Kenji Taniguchi, Meiri Shida-Kawazoe, Shoichi Metsugi, Taro Miyazaki, Naoko A. Wada, Yuki Ohte, Shun Shimizu, Hirofumi Mikami, Tatsuhiko Tachibana, Natsuki Ono, Kenji Adachi, Tetsushi Sakiyama, Tomochika Matsushita, Shojiro Kadono, Shun-ichiro Komatsu, Akihisa Sakamoto, Sayuri Horikawa, Ayano Hirako, Koki Hamada, Sotaro Naoi, Nasa Savory, Yasuko Satoh, Motohiko Sato, Yuki Noguchi, Junko Shinozuka, Haruka Kuroi, Ami Ito, Tetsuya Wakabayashi, Masaki Kamimura, Fumihisa Isomura, Yasushi Tomii, Noriaki Sawada, Atsuhiko Kato, Otoya Ueda, Yoshito Nakanishi, Mika Endo, Kou-ichi Jishage, Yoshikii Kawabe, Takehisa Kitazawa, Tomoyuki Igawa
Summary: The novel anti-CD137 switch antibody STA551 shows strong and broad antitumor efficacy by targeting extracellular ATP in the tumor microenvironment, providing a potential treatment option for a wide variety of cancers regardless of antigen expression. The antibody demonstrates potent tumor inhibition without systemic toxicity or dependence on antigen expression in both mouse and human tumor models, supporting its further clinical testing and potential application to other cancer therapy targets.
Article
Medicine, Research & Experimental
Yu-Heng Vivian Ma, Amanda Sparkes, Ema Romao, Shrayasee Saha, Jean Gariepy
Summary: Novel murine anti-human VISTA monoclonal antibodies, nanobodies, and cross-reactive rat anti-murine/human VISTA antibodies were developed. These agonistic VISTA antibodies have the potential to treat inflammatory disorders.
Article
Multidisciplinary Sciences
Javier Glez-Vaz, Arantza Azpilikueta, Maria C. Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri-Rey, Maite alvarez, Jose. L. L. Perez-Gracia, Sergio Ciordia, Inaki Eguren-Santamaria, Raluca Alexandru, Pedro Berraondo, Carlos de Andrea, Alvaro Teijeira, Fernando Corrales, Juan. M. M. Zapata, Ignacio Melero
Summary: CD137 is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). The physical association between cIAP1/cIAP2 and the CD137 signaling complex is demonstrated. cIAPs are required for CD137 signaling towards NF-κB and MAPK pathways, and for the costimulation of human and mouse T lymphocytes.
Article
Veterinary Sciences
Artur Summerfield, Heidi Gerber, Rebeka Schmitt, Matthias Liniger, Santina Grazioli, Emiliana Brocchi
Summary: This study demonstrates that monoclonal antibodies targeting FMDV O and A serotypes are able to opsonize the virus and induce cell death. Opsonization shows broader reactivity within the serotype and correlates better with vaccine dose compared to neutralization. Neutralization and opsonization titers are similarly predictive of protection.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Gilles Thibault, Gilles Paintaud, Hsueh Cheng Sung, Laurie Lajoie, Edouard Louis, Celine Desvignes, Herve Watier, Valerie Gouilleux-Gruart, David Ternant
Summary: Fc gamma RIIA/CD32A is expressed on platelets and some endothelial cells, playing a role in binding IgG antibodies, which may contribute to their elimination. Platelet Fc gamma RIIA's affinity for different IgG subclasses influences the clearance of antibodies like infliximab.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Shlomo Elias, Inbal Kol, Shira Kahlon, Rajaa Amore, Mariam Zeibak, Dror Mevorach, Uriel Elchalal, Orly Zelig, Ofer Mandelboim
Summary: Anti-RhD antibodies are used to prevent RhD immunization, potentially by inducing NK cell degranulation. The mechanism involves CD16 activation and glycosylation of the antibodies. Additionally, the RhD drug may enhance killing of dendritic cells.
Article
Biotechnology & Applied Microbiology
Qiong Wang, Tiexin Wang, Roushu Zhang, Shuang Yang, Kevin S. McFarland, Cheng-Yu Chung, Hongpeng Jia, Lai-Xi Wang, John F. Cipollo, Michael J. Betenbaugh
Summary: This study investigates the impact of N-glycan pattern on the quality and function of IgG antibodies, and explores the methods of glycoengineering and protein engineering to modify these effects. The results show that glycoengineering and protein engineering can alter the glycan composition and structure of antibodies, thereby affecting their effector functions such as cytotoxicity and cellular adhesion. Additionally, the study reveals that different glycan compositions and structures have different effects on the cytotoxicity and cellular adhesion of antibodies.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Chemistry, Multidisciplinary
Chong Ou, Sunaina Kiran Prabhu, Xiao Zhang, Guanghui Zong, Qiang Yang, Lai-Xi Wang
Summary: Monoclonal antibodies are rapidly growing in use for cancer, infectious, and autoimmune disease treatment. A chemoenzymatic synthesis method was developed to create structurally well-defined conjugates of antibodies with rhamnose and alpha Gal trisaccharide clusters, enhancing targeted cell killing through CDC. These antibody-rhamnose cluster conjugates showed potent CDC activity for cancer cell killing compared to the antibody-alpha Gal trisaccharide cluster conjugates.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Beatriz Trastoy, Jonathan J. Du, Mikel Garcia-Alija, Chao Li, Erik H. Klontz, Lai-Xi Wang, Eric J. Sundberg, Marcelo E. Guerin
Summary: This article discusses the molecular mechanism by which ENGases recognize different N-glycans and protein substrates, especially those specific for IgG antibodies. This understanding can rationalize the glycoengineering of immunotherapeutic antibodies and enhance their impact on the treatment of various diseases.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiao Zhang, Huiying Liu, Jia He, Chong Ou, Thomas C. Donahue, Musleh M. Muthana, Lishan Su, Lai-Xi Wang
Summary: A chemoenzymatic method enables efficient and site-specific conjugation of high-affinity M6P glycan ligands to antibodies, resulting in structurally well-defined antibody-M6P glycan conjugates. This method has potential applications for targeted degradation of membrane-associated proteins.
ACS CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mikel Garcia-Alija, Jonathan J. Du, Izaskun Ordonez, Asier Diz-Vallenilla, Alicia Moraleda-Montoya, Nazneen Sultana, Chau G. Huynh, Chao Li, Thomas Connor Donahue, Lai-Xi Wang, Beatriz Trastoy, Eric J. Sundberg, Marcelo E. Guerin
Summary: This study presents the crystal structures of the multi-domain glycoside hydrolase EndoE from the human pathogen Enterococcus faecalis and provides insights into its substrate specificity and catalytic mechanism. EndoE combines two enzyme domains with distinct functions and glycan specificities to play a dual role in glycan metabolism and immune evasion.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Thomas C. Donahue, Guanghui Zong, Nicholas A. O'Brien, Chong Ou, Jeffrey C. Gildersleeve, Lai-Xi Wang
Summary: N-Glycosylation plays an important role in biological recognition, but there are very few specific antibodies available for research and treatment. In this study, phage Q beta conjugates with representative N-glycans were synthesized to raise N-glycan-specific antibodies. However, most of the antibodies recognized the shared chitobiose core instead of specific N-glycan structures. The linker chemistry and sialylation of N-glycans were found to affect antibody specificity. Adipic acid-linked N-glycan-Q beta immunogens raised antibodies capable of recognizing both the N-acetylglucosamine moieties of the chitobiose core, while triazole-linked immunogens preferentially recognized the innermost N-acetylglucosamine moiety. Furthermore, the presence of sialylation significantly suppressed the immune response. These findings highlight the challenges in eliciting mammalian N-glycan-specific antibodies through conventional vaccine design and immunization.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jinyang Li, Zhiling Zhao, Eunkyoung Kim, John R. Rzasa, Guanghui Zong, Lai-Xi Wang, William E. Bentley, Gregory F. Payne
Summary: Recent observations suggest that abiotic materials can engage in interactive communication through redox reactions. In this study, a hydrogel made from four-armed thiolated polyethylene glycol (PEG-SH) and the bacterial metabolite pyocyanin (PYO) was fabricated and shown to exhibit reversible redox activity. The study also highlighted the significance of the redox network's topology in controlling molecular switching and electron flow within the hydrogel.
Article
Biochemistry & Molecular Biology
Chong Ou, Chao Li, Chiguang Feng, Xin Tong, Gerardo R. Vasta, Lai-Xi Wang
Summary: A facile synthesis of beta-cyclodextrin-based multivalent ligands containing Tn and TF antigens was reported. These synthetic multivalent glycan ligands demonstrated enhanced binding affinity and clustering effect in binding to human Gal-3. The GalNAc-containing heptavalent ligand showed the highest affinity and the synthetic ligands could efficiently inhibit Gal-3 binding to human airway epithelial cells.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kun Huang, Chao Li, Guanghui Zong, Sunaina Kiran Prabhu, Digantkumar G. Chapla, Kelley W. Moremen, Lai-Xi Wang
Summary: This study describes the first in vitro enzymatic sulfation of biantennary complex type N-glycans using recombinant human CHST2. The sulfotransferase demonstrated high antennary preference and selectively sulfated the GlcNAc moiety on the Man alpha 1,3Man arm of the biantennary N-glycan. The sulfated N-glycans were further elongated and transferred to intact antibodies using a chemoenzymatic method, resulting in homogeneous sulfated glycoforms. Sulfation did not affect the binding affinity of the antibody for Fc gamma IIIa receptor.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemical Research Methods
Thomas C. Donahue, Guanghui Zong, Chong Ou, Philip DeShong, Lai -Xi Wang
Summary: In this study, catanionic vesicles were used as a stable lipid-based nanoparticle scaffold for displaying multivalent glycans, which showed enhanced affinity for lectins and could be used for drug delivery and intervention of protein-carbohydrate interactions implicated in disease.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rosa L. Cordeiro, Camila R. Santos, Mariane N. Domingues, Tatiani B. Lima, Renan A. S. Pirolla, Mariana A. B. Morais, Felippe M. Colombari, Renan Y. Miyamoto, Gabriela F. Persinoti, Antonio C. Borges, Marcelo A. de Farias, Fabiane Stoffel, Chao Li, Fabio C. Gozzo, Marin van Heel, Marcelo E. Guerin, Eric J. Sundberg, Lai-Xi Wang, Rodrigo V. Portugal, Priscila O. Giuseppe, Mario T. Murakami
Summary: This study elucidated the key biochemical steps and molecular mechanisms by which Bifidobacterium longum utilizes high-mannose N-glycans, providing insights into the utilization of this perennial carbon and energy source in the intestinal lumen.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Kevin S. Kao, Aaron Gupta, Guanghui Zong, Chao Li, Isabell Kerschbaumer, Sara Borghi, Jacqueline M. Achkar, Stylianos Bournazos, Lai-Xi Wang, Jeffrey V. Ravetch
Summary: This article describes a method to identify and characterize nanobodies that can distinguish specific glycoforms, which is useful for studying protein glycosylation. The method allows for clinical stratification of infected individuals and disruption of specific immune responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Miloslav Sanda, Yang Qiang, Zong Guanghui, Chen He, Zheng Zhihao, Harmeet Dhani, Khalid Khan, Alexander Kroemer, Wang Lai-Xi, Radoslav Goldman
Summary: Targeted quantification of glycoproteins has been limited by the lack of optimized workflows and isotopically labeled standards. In this study, a streamlined chemoenzymatic synthesis of isotopically labeled glycopeptides of IgG1 was introduced for quantification in an energy optimized LC-MS/MS-PRM workflow. The incorporation of stable isotope labeled N-acetylglucosamine enabled efficient monitoring of glycopeptide fragment ions, resulting in reduced quantification variability and higher sensitivity compared to traditional workflows. Rapid quantification of IgG1 Fc glycoforms from COVID-19 patients was successfully demonstrated.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Thomas C. Donahue, Chong Ou, Qiang Yang, Robin Flinko, Xiao Zhang, Guanghui Zong, George K. Lewis, Lai-Xi Wang
Summary: Targeted degradation using cell-specific lysosome targeting receptors is a new therapeutic strategy for eliminating disease-associated proteins. This study focuses on using the liver-specific human asialoglycoprotein receptor (ASGPR) for targeted protein degradation (TPD). The efficiency of different glycan ligands for ASGPR-mediated lysosomal delivery is investigated, and chemoenzymatic Fc glycan remodeling is employed for constructing antibody-ligand conjugates. The results show that the nature of the glycan ligands and the spacer length in the conjugates are critical for receptor binding and degradation of disease-associated proteins.
ACS CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Analytical
Diana Campos, Michael Girgis, Qiang Yang, Guanghui Zong, Radoslav Goldman, Lai-Xi Wang, Miloslav Sanda
Summary: Mass spectrometry can provide valuable insights into glycosylation analysis, but analyzing isobaric glycopeptide structures remains challenging. Modulating collision energy can improve structural elucidation, especially for qualitative purposes. Our research identified the potential for false-positive structure assignments and established a minimum intensity threshold to prevent misidentification of structure-specific fragments in glycoproteomics analysis.
ANALYTICAL CHEMISTRY
(2023)