Article
Immunology
Chunyu Liu, Chuanfei Yu, Yalan Yang, Jing Huang, Xiaojuan Yu, Maoqin Duan, Lang Wang, Junzhi Wang
Summary: In this study, an engineered monoclonal Jurkat/NFAT/CD32a-Fc epsilon RI gamma effector cell line was developed to measure the bioactivity of antibody-dependent cellular phagocytosis (ADCP). The bioassay was optimized using a Design of Experiment (DoE) strategy and fully validated according to ICH-Q2(R1) to demonstrate good performance characteristics. The established bioassay can be applied to evaluate the ADCP bioactivity for anti-CD20 mAbs and potentially for mAbs targeting other antigens.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Capucine L. Grandjean, Zacarias Garcia, Fabrice Lemaitre, Beatrice Breart, Philippe Bousso
Summary: It was found that macrophages in the bone marrow are the main way to eliminate tumors, but they can only act on neighboring tumors and have a limited active time.
Article
Immunology
Justin Pollara, Matthew Zirui Tay, R. Whitney Edwards, Derrick Goodman, Andrew R. Crowley, Robert J. Edwards, David Easterhoff, Haleigh E. Conley, Taylor Hoxie, Thaddeus Gurley, Caroline Jones, Emily Machiele, Marina Tuyishime, Elizabeth Donahue, Shalini Jha, Rachel L. Spreng, Thomas J. Hope, Kevin Wiehe, Max M. He, M. Anthony Moody, Kevin O. Saunders, Margaret E. Ackerman, Guido Ferrari, Georgia D. Tomaras
Summary: The study found differences in ADP activity between humans and macaques, but certain engineered antibodies can effectively enhance ADP activity in both species. These results contribute to a better translation of human and macaque antibody and FcR biology, and may help to improve testing accuracy and evaluations of future prevention strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Jack M. Edwards, Behnaz Heydarchi, Georges Khoury, Natalia A. Salazar-Quiroz, Christopher A. Gonelli, Bruce Wines, P. Mark Hogarth, Anne B. Kristensen, Matthew S. Parsons, Damian F. J. Purcell
Summary: The study successfully enhanced the Fc-mediated effector functions of the bovine-human chimeric bNAb NC-Cow1 with an ultralong CDRH3, improving neutralization activity and cell potency against HIV-1 while maintaining envelope binding. This research is significant for the development of multifunctional anti-HIV antibodies and enhancing prevention of HIV-1 transmission.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Bruce D. Wines, Halina M. Trist, Sandra Esparon, Rachael E. Impey, Graham A. Mackay, Robert K. Andrews, Tatiana P. Soares da Costa, Geoffrey A. Pietersz, Ross Baker, P. Mark Hogarth
Summary: The activation of Fc gamma RIIa by monoclonal antibodies requires interaction with both the Fab and Fc regions simultaneously on the same receptor molecules.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yuanling Yu, Meiyu Wang, Xiaoai Zhang, Shufen Li, Qingbin Lu, Haolong Zeng, Hongyan Hou, Hao Li, Mengyi Zhang, Fei Jiang, Jiajing Wu, Ruxia Ding, Zehua Zhou, Min Liu, Weixue Si, Tao Zhu, Hangwen Li, Jie Ma, Yuanyuan Gu, Guangbiao She, Xiaokun Li, Yulan Zhang, Ke Peng, Weijin Huang, Wei Liu, Youchun Wang
Summary: ADCC responses are antibody-regulated immune responses mediated through the Fc fragment, and it is unclear if they contribute to COVID-19 disease development. Interestingly, patients with severe COVID-19 had higher ADCC activities, with recovered patients showing higher levels than deceased patients. This highlights ADCC as a major trait of COVID-19 patients with potential implications for neutralization levels against the virus.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Hematology
Mitchell Evers, Thies Roesner, Anna Duenkel, J. H. Marco Jansen, Niklas Baumann, Toine Ten Broeke, Maaike Nederend, Klara Eichholz, Katja Klausz, Karli Reiding, Denis M. Schewe, Christian Kellner, Matthias Peipp, Jeanette H. W. Leusen, Thomas Valerius
Summary: Blocking the CD47-SIRPa axis enhances the killing of lymphoma cells by myeloid effector cells, particularly in the presence of CD20 antibodies. CD20 antibodies of human IgA2 isotype variants mediate ADCP and ADCC, with enhanced efficacy when combined with CD47-blocking antibodies or other inhibition methods. OBI-IgA2 is consistently more potent than RTX-IgA2 and OFA-IgA2, showing therapeutic effectiveness in vivo and in vitro.
Article
Multidisciplinary Sciences
Xiaojie Yu, Christian M. Orr, H. T. Claude Chan, Sonya James, Christine A. Penfold, Jinny Kim, Tatyana Inzhelevskaya, C. Ian Mockridge, Kerry L. Cox, Jonathan W. Essex, Ivo Tews, Martin J. Glennie, Mark S. Cragg
Summary: Low affinity of immunomodulatory antibodies leads to greater activity through increased clustering, resulting in higher immune cell activation, T cell expansion, and antitumor activity. This discovery reveals a new mechanism for enhancing receptor activation across diverse receptor families and sheds light on the mechanism of antibody-mediated receptor signaling. Affinity engineering offers a rational, efficient, and tunable solution for delivering antibody-mediated receptor activity for the treatment of human disease.
Article
Biochemistry & Molecular Biology
Simone Eberhard, Hannes Vietzen, Irene Goerzer, Peter Jaksch, Elisabeth Puchhammer-Stoeckl
Summary: The study found that a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection, especially after receiving a lung transplant from an HCMV-positive donor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
William R. Wonderly, Daniel G. DeMartini, Saeed Najafi, Marcela Areyano, Joan-Emma Shea, J. Herbert Waite
Summary: This study investigates the contribution of intramolecular crosslinks in polymeric materials to mechanical properties using the tethering threads of Octopus bimaculoides egg cases. The presence of regularly spaced disulfide linkages in the load-bearing fibers improves stiffness, toughness, and energy dissipation. Molecular dynamics and X-ray scattering reveal that the EGF-like domains deform by recruiting hidden length beta-sheet structures between the disulfides. This study enhances our understanding of intramolecular crosslinking in polymers and provides insights into the mechanical contributions of EGF domains in the extracellular matrix.
Article
Immunology
Tobias Zeller, Sebastian Lutz, Ira A. Muennich, Roland Windisch, Patricia Hilger, Tobias Herold, Natyra Tahiri, Jan C. Banck, Oliver Weigert, Andreas Moosmann, Michael Von Bergwelt-Baildon, Cindy Flamann, Heiko Bruns, Christian Wichmann, Niklas Baumann, Thomas Valerius, Denis M. Schewe, Matthias Peipp, Thies Roesner, Andreas Humpe, Christian Kellner
Summary: Blocking both CD47 and LILRB1 can enhance the phagocytosis of lymphoma cells by macrophages, improving the efficacy of antibody therapy for chronic lymphocytic leukemia and lymphomas.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Kate E. Mastraccio, Celeste Huaman, Si'Ana A. Coggins, Caitlyn Clouse, Madeline Rader, Lianying Yan, Pratyusha Mandal, Imran Hussain, Anwar E. Ahmed, Trung Ho, Austin Feasley, Bang K. Vu, Ina L. Smith, Wanda Markotter, Dawn L. Weir, Eric D. Laing, Christopher C. Broder, Brian C. Schaefer
Summary: Rabies is a fatal viral disease of humans, but this study demonstrates that a single-dose monoclonal (mAb) therapy can lead to a functional cure even after robust replication in the CNS. The therapeutic efficacy of F11, a human IgG1 antibody, requires a functional Fc region, suggesting the involvement of immune cells bearing FcR gamma. The effectiveness of F11 depends on the intact host adaptive immune response, particularly CD4 T cells. The administration of F11 alters the proportions and phenotypes of immune cells in the brain, and although the virus persists at a low level, the animals remain free of disease signs.
EMBO MOLECULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Vivekananda Kedage, Diego Ellerman, Mingjian Fei, Wei-Ching Liang, Gu Zhang, Eric Cheng, Juan Zhang, Yongmei Chen, Haochu Huang, Wyne P. Lee, Yan Wu, Minhong Yan
Summary: This study describes a bispecific antibody approach that utilizes CLEC5A to drive Fc gamma receptor-independent phagocytosis, potentially overcoming the negative impact of Fc gamma RIIB. The results demonstrate the effectiveness of this approach for tumor treatment.
Article
Oncology
Stephanie Durand-Panteix, Jacques Monteil, Magali Sage, Armand Garot, Marie Clavel, Amal Saidi, Julien Torgue, Michel Cogne, Isabelle Quelven
Summary: This study investigated the potential of alpha-RIT in combination with Pb-212-rituximab for NHL treatment using mouse lymphoma cells. Results showed significant tumor regression and increased survival using 277.5 kBq Pb-212-rituximab, highlighting the potency of alpha-RIT for NHL treatment.
BRITISH JOURNAL OF CANCER
(2021)
Article
Virology
Ahmed M. Khalil, Michael S. Piepenbrink, Ian Markham, Madhubanti Basu, Luis Martinez-Sobrido, James J. Kobie
Summary: IBV contributes significantly to morbidity and mortality, particularly in children, necessitating improvements in vaccines and treatments. A specific hMAb, 1092D4, has been found to have minimal dependence on Fc-effector functions for in vivo antiviral activity.