Article
Immunology
Zhaoliang Huang, Xinghua Pang, Tingting Zhong, Tailong Qu, Na Chen, Shun Ma, Xinrong He, Dennis Xia, Max Wang, Michelle Xia, Baiyong Li
Summary: Penpulimab, an IgG1 backbone anti-PD-1 antibody, has demonstrated good stability and reduced host cell protein residue. Fc engineering has eliminated Fc-mediated effector functions, including ADCC and ADCP, and reduced ADCR, contributing to its more favorable safety profile.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Angela I. Schriek, Marlies M. van Haaren, Meliawati Poniman, Gillian Dekkers, Arthur E. H. Bentlage, Marloes Grobben, Gestur Vidarsson, Rogier W. Sanders, Theo Verrips, Teunis B. H. Geijtenbeek, Raimond Heukers, Neeltje A. Kootstra, Steven W. de Taeye, Marit J. van Gils
Summary: Broadly neutralizing nanobodies targeting HIV-1 envelope glycoprotein, combined with IgG1 Fc fusion, have been studied as alternative treatments. The study found that multivalent nanobodies coupled with long linkers showed increased neutralization potency. Fusion of IgG1 Fc domain to nanobodies not only improved neutralization potency but also restored Fc-mediated antibody effector functions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Christine Baksmeier, Pat Blundell, Julia Steckel, Verena Schultz, Quan Gu, Ana Da Silva Filipe, Alain Kohl, Chris Linnington, Dongli Lu, Anne Dell, Stuart Haslam, Jiabin Wang, Dan Czajkowsky, Norbert Goebels, Richard J. Pleass
Summary: IVIG is an established treatment for autoimmune conditions, but mechanisms of action remain unclear. This study used adapted Fc fragments to dissect IVIG effector mechanisms in an ex vivo model of demyelination. The protective effects of the adapted Fc fragments were dose-dependent and attributed to interference with complement-mediated damage to oligodendrocytes. Overall, findings suggest that recombinant biomimetics may be more effective than IVIG in controlling demyelination.
Article
Immunology
Pengcheng Zuo, Yaopeng Li, Chi He, Tantan Wang, Xu Zheng, Hao Liu, Zhen Wu, Junting Zhang, Xuebin Liao, Liwei Zhang
Summary: This study evaluated the anti-tumor activity and safety of GD2-CAR NK-92 cells for the treatment of DIPG. Results showed that GD2-CAR NK-92 cells effectively killed DIPG cells with high GD2 expression and inhibited tumor growth in vivo, but had limited activity against DIPG cells with low GD2 expression. Further clinical trials are needed to demonstrate the safety and anti-tumor effect of this therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Jue Zhang, Sarah Webster, Bret Duffin, Matthew N. Bernstein, John Steill, Scott Swanson, Matthew H. Forsberg, Jennifer Bolin, Matthew E. Brown, Aditi Majumder, Christian M. Capitini, Ron Stewart, James A. Thomson, Igor I. Slukvin
Summary: In this study, anti-GD2 CAR was integrated into the AAVS1 locus of human pluripotent stem cells using CRISPR-Cas9 gene editing. A serum- and feeder-free differentiation protocol was established to generate CAR macrophages (CAR-Ms) through arterial endothelial-to-hematopoietic transition (EHT). The CAR-Ms produced using this method showed potent cytotoxic activity against GD2-expressing neuroblastoma and melanoma in vitro and neuroblastoma in vivo. This study provides a new platform for efficient generation of off-the-shelf CAR-Ms for antitumor immunotherapy.
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
Biochemistry & Molecular Biology
Andras Heczey, Xin Xu, Amy N. Courtney, Gengwen Tian, Gabriel A. Barragan, Linjie Guo, Claudia Martinez Amador, Nisha Ghatwai, Purva Rathi, Michael S. Wood, Yanchuan Li, Chunchao Zhang, Thorsten Demberg, Erica J. Di Pierro, Andrew C. Sher, Huimin Zhang, Birju Mehta, Sachin G. Thakkar, Bambi Grilley, Tao Wang, Brian D. Weiss, Antonino Montalbano, Meena Subramaniam, Chenling Xu, Chirag Sachar, Daniel K. Wells, Gianpietro Dotti, Leonid S. Metelitsa
Summary: This study presented updated interim results on the evaluation of GD2-specific CAR-expressing NKT cells co-expressing IL15 in children with NB. The results showed that GD2-CAR.15 NKT cells had anti-tumor activity, which could be enhanced by targeting BTG1.
Article
Multidisciplinary Sciences
Babak Moghimi, Sakunthala Muthugounder, Samy Jambon, Rachelle Tibbetts, Long Hung, Hamid Bassiri, Michael D. Hogarty, David M. Barrett, Hiroyuki Shimada, Shahab Asgharzadeh
Summary: The study highlights the importance of developing gated systems for predicting clinical toxicity of CAR T cells in solid tumors. By utilizing murine and human CAR-T cells specific for tumor antigens, the researchers were able to generate a GD2-B7H3 CAR-T with improved metabolic fitness and efficacy in controlling neuroblastoma growth in preclinical models. This innovative approach shows promising results in suppressing neuroblastoma with minimal adverse effects.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Rui Duan, Yan Liu, Dongmei Tang, Run Lin, Jinrong Huang, Ming Zhao
Summary: It has been established that atherosclerosis is an autoimmune disease, but the role of FcεRIIA in atherosclerosis is not well understood. This study investigates the relationship between FcεRIIA genotypes and the effectiveness of different IgG subclasses in treating atherosclerosis. The findings suggest that IgG1 is the optimal subtype for treating atherosclerosis, as it can induce monocyte/macrophage polarization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nanoscience & Nanotechnology
Liyu Zhang, Meng Wang, Zeen Zhu, Chenxi Ding, Shengquan Chen, Haibin Wu, Ying Yang, Fengyu Che, Qiao Li, Hui Li
Summary: The study utilized aptamers to construct a pH-sensitive drug delivery system, which could precisely deliver drugs to tumor cells for tumor inhibition while protecting normal cells.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Oncology
Nikolai Siebert, Justus Leopold, Maxi Zumpe, Sascha Troschke-Meurer, Simon Biskupski, Alexander Zikoridse, Holger N. Lode
Summary: Treatment with the anti-GD(2) antibody dinutuximab beta (DB) can improve the survival of high-risk neuroblastoma (NB) patients by 15%. In this study, a DB-based immunotherapy combined with the immunocytokine FAP-IL-2v was investigated as an alternative to IL-2 treatment. The combination therapy enhanced ADCC and reduced Treg cell induction, resulting in reduced tumor growth and improved survival in a murine NB model.
Article
Hematology
Thijs L. J. van Osch, Janita J. Oosterhoff, Arthur E. H. Bentlage, Jan Nouta, Carolien A. M. Koeleman, Dionne M. Geerdes, Juk Yee Mok, Sebastiaan Heidt, Arend Mulder, Wim J. E. van Esch, Rick Kapur, Leendert Porcelijn, Ellen van der Schoot, Masja de Haas, Manfred Wuhrer, Jan Voorberg, Gestur Vidarsson
Summary: Approximately 20% of patients receiving multiple platelet transfusions develop platelet alloantibodies, which can lead to platelet refractoriness. Factors such as antibody glycosylation and the breadth of the polyclonal immune response may affect complement activation and clearance of donor platelets.
Article
Immunology
Alyson J. Smith, Robert E. Thurman, Weiping Zeng, Bryan Grogan, Sasha Lucas, Guadalupe Gutierrez, Ryan A. Heiser, Serena W. Wo, Amber Blackmarr, Scott Peterson, Shyra J. Gardai
Summary: TIGIT, an immune checkpoint receptor, has potential applications in anti-tumor therapies. The Fc backbone of anti-TIGIT monoclonal antibodies plays a crucial role in their anti-tumor activity, and nonfucosylation of the backbone enhances this activity. These findings highlight the importance of the Fc backbone in the anti-tumor activity of anti-TIGIT antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Jerome Egli, Stefan Heiler, Felix Weber, Guido Steiner, Timo Schwandt, Katharine Bray-French, Christian Klein, Sebastian Fenn, Gregor P. Lotz, Eugenia Opolka-Hoffmann, Thomas E. Kraft, Laetitia Petersen, Rebecca Moser, Jonathan DeGeer, Michel Siegel, Daniela Finke, Juliana Bessa, Antonio Iglesias
Summary: Clinical anti-drug-antibody responses pose challenges to therapeutic antibody development. Enhanced production of anti-idiotypic antibodies against cancer immunotherapy antibodies can affect efficacy and safety. Through studying transgenic mice, it was found that neonatal Fc receptor plays a role in maintaining tolerance to non-germline encoded idiotype. Additionally, the incorporation of T cell-engaging moieties can trigger undesired immune responses.
Article
Oncology
Guangji Zhang, Yu Zhao, Zhongfeng Liu, Weihua Liu, Huantong Wu, Xuan Wang, Zhiguo Chen
Summary: This study found that the combination therapy of GD2 CAR-T and Nivolumab may offer an improved therapeutic strategy for the treatment of glioblastoma (GBM) by enhancing cytotoxicity, reducing T cell exhaustion, and preventing neurotoxicity.
TRANSLATIONAL ONCOLOGY
(2023)