Article
Hematology
Lindsay Hammons, Shabi Haider, Andrew J. Portuguese, Rahul Banerjee, Aniko Szabo, Marcelo Pasquini, Saurabh Chhabra, Sabarinath Radhakrishnan, Meera Mohan, Ravi Narra, Jing Dong, Siegfried Janz, Nirav N. Shah, Mehdi Hamadani, Anita D'Souza, Parameswaran Hari, Binod Dhakal
Summary: CAR-T and BsAb therapies are feasible, safe, and provide deep and durable responses in MM patients with a prior history of allo-HCT.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cell Biology
Roeland Lameris, Jurjen M. Ruben, Victoria Iglesias-Guimarais, Milon de Jong, Myrthe Veth, Fleur S. van de Bovenkamp, Iris de Weerdt, Arnon P. Kater, Sonja Zweegman, Sjeng Horbach, Thilo Riedl, Benjamin Winograd, Rob C. Roovers, Anton E. P. Adang, Tanja D. de Gruijl, Paul W. H. I. Parren, Hans J. van der Vliet
Summary: The Vy9V52-T cell engagers have the potential to achieve high therapeutic efficacy with limited toxicity by activating type 1 NKT cells and Vy9V52-T cells to produce strong proinflammatory cytokines and induce target cell lysis. These engagers have shown improved survival in AML, MM, and T-ALL mouse models. The CD1d-V52 engager is currently being evaluated in a phase 1/2a study in patients with therapy refractory CLL, MM, or AML.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Nanna Skeltved, Mie A. A. Nordmaj, Nicolai T. T. Berendtsen, Robert Dagil, Emilie M. R. Stormer, Nader Al-Nakouzi, Ke Jiang, Alexandra Aicher, Christopher Heeschen, Tobias Gustavsson, Swati Choudhary, Ismail Gogenur, Jan P. P. Christensen, Thor G. G. Theander, Mads Daugaard, Ali Salanti, Morten A. A. Nielsen
Summary: The malaria protein VAR2CSA has anti-tumor efficacy by binding to oncofetal chondroitin sulfate (ofCS). Combining V-aCD3 with an immune checkpoint inhibitor enhances the anti-tumor effects, leading to complete elimination of solid tumors in mice.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Hematology
Daniele Caracciolo, Nicoletta Polera, Beatrice Belmonte, Francesco Conforti, Stefania Signorelli, Alessandro Gulino, Nicoletta Staropoli, Franca Maria Tuccillo, Patrizia Bonelli, Giada Juli, Katia Grillone, Serena Ascrizzi, Maria Cirillo, Leonardo Migale, Andrea Ballerini, Cristina Pelizon, Maria Teresa Di Martino, Pierosandro Tagliaferri, Caterina Riillo, Pierfrancesco Tassone
Summary: UMG1 is a unique epitope of CD43, expressed in thymocytes and a minority of peripheral blood T lymphocytes, and highly expressed in DLBCL. Targeting UMG1 with UMG1/CD3 epsilon-BTCE induces cytotoxicity against DLBCL cells and shows synergy with lenalidomide, suggesting its potential as a therapeutic for DLBCL.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Elizabeth Pham, Matthias Friedrich, Famke Aeffner, Michael Lutteropp, Natalie F. Mariano, Petra Deegen, Christoph Dahlhoff, Franziska Vogel, Claudia Bluemel, John M. Harrold, Christian Brandl, Natalia Grinberg, Benno Rattel, Angela Coxon, Julie M. Bailis
Summary: MUC12, highly expressed in colorectal tumors but restricted in normal tissues, is a potential therapeutic target for BiTE molecules. However, high doses of BiTE targeting MUC12 may lead to on-target toxicity, as shown in current studies.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Oncology
Shujie Zhou, Mingguo Liu, Fei Ren, Xiangjiao Meng, Jinming Yu
Summary: T cell-based immunotherapies have revolutionized cancer treatment, but limited T-cell infiltration in tumor sites remains a major issue. BiTE therapy, a promising approach using bispecific antibodies to induce tumor lysis, has shown impressive efficacy in B cell malignancies but faces resistance mechanisms such as antigen loss and immune checkpoints upregulation. This highlights the need for modifying antibody constructs and developing combination strategies to enhance efficacy and reduce toxicity, particularly in solid tumors where response to BiTE therapy is poor.
BIOMARKER RESEARCH
(2021)
Article
Oncology
Alexander Sternjak, Fei Lee, Oliver Thomas, Mercedesz Balazs, Joachim Wahl, Grit Lorenczewski, Ines Ullrich, Markus Muenz, Benno Rattel, Julie M. Bailis, Matthias Friedrich
Summary: AMG 596 is a potential drug for GBM treatment with highly specific and potent T-cell activation capabilities, increasing survival rate in mice and showing promising preclinical efficacy.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Immunology
Ewa Kubicka, Lawrence G. Lum, Manley Huang, Archana Thakur
Summary: The study demonstrates that arming activated T cells (ATCs) with bispecific antibodies (BiAbs) can effectively target and lyse acute myeloid leukemia (AML) cells and leukemic stem cells (LSCs), providing a potent and non-toxic therapeutic strategy to enhance chemo-responsiveness in older patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Xinghui Xiao, Ying Cheng, Xiaodong Zheng, Yuhang Fang, Yu Zhang, Rui Sun, Zhigang Tian, Haoyu Sun
Summary: Bispecific antibodies that target CD3 have been widely used in tumor treatment, but may cause severe side effects. Our study developed two IgG-like bispecific antibodies, BK1 and BT1, which targeted NK cells and T cells, respectively. It was found that BK1 had a stronger antitumor effect and induced fewer proinflammatory cytokines compared to BT1. Combining BK1 with BT1 further reduced cytokine secretion by T cells, suggesting a promising future for NK-cell engagers in clinical settings.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Satoko Kakiuchi-Kiyota, Thorsten Ross, Heidi Ackerly Wallweber, James R. Kiefer, Melissa M. Schutten, Adeyemi O. Adedeji, Hao Cai, Robert Hendricks, Sivan Cohen, Srividya Myneni, Luna Liu, Aaron Fullerton, Nicholas Corr, Lanlan Yu, Denise de Almeida Nagata, Shelly Zhong, Steven R. Leong, Ji Li, Rin Nakamura, Teiko Sumiyoshi, Jinze Li, Ayse Meric Ovacik, Bing Zheng, Mike Dillon, Christoph Spiess, Susanne Wingert, Erich Rajkovic, Kristina Ellwanger, Uwe Reusch, Andrew G. Polson
Summary: Despite the current incurability of multiple myeloma (MM), the novel treatment, RO7297089, shows potential as an effective and well-tolerated therapy. By targeting BCMA and CD16A, RO7297089 induces lysis of MM cells and has a favorable safety profile, as evidenced by in vitro cytokine release and animal studies.
Article
Biology
Fanlin Li, Wei Xu, Xiaoqing Zhang, Wanting Wang, Shan Su, Ping Han, Haiyong Wang, Yanqin Xu, Min Li, Lilv Fan, Huihui Zhang, Qiang Dai, Hao Lin, Xinyue Qi, Jie Liang, Xin Wang, Shibo Jiang, Youhua Xie, Lu Lu, Xuanming Yang
Summary: Neutralizing antibodies are not as effective in therapeutic models as in prophylactic models due to limited efficacy in eliminating virus-producing cells. A SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy is presented, which blocks viral entry and eliminates infected cells through T cell-mediated cytotoxicity. S-BiTE is effective against both original and Delta variants of SARS-CoV-2, suggesting potential application against immune-escaping variants. In a humanized mouse model with live SARS-CoV-2 infection, S-BiTE significantly reduces viral load compared to neutralization treatment only.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Saru Basnet, Joao M. Santos, Dafne C. A. Quixabeira, James H. A. Clubb, Susanna A. M. Gronberg-Vaha-Koskela, Victor Arias, Santeri Pakola, Tatiana V. Kudling, Camilla Heinio, Riikka Havunen, Victor Cervera-Carrascon, Suvi Sorsa, Marjukka Anttila, Anna Kanerva, Akseli Hemminki
Summary: This study introduces a novel oncolytic adenovirus, TILT-321, which can replicate in cancer cells and produce a high concentration of aMUC1aCD3 molecules. TILT-321 demonstrated efficient tumor cell lysis and enhanced T cell activity in vitro and in a mouse model. The results provide a proof of concept for an effective strategy to overcome limitations in delivering bispecific T cell engagers for solid tumor treatment.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Multidisciplinary Sciences
Katarzyna C. Pituch, Markella Zannikou, Liliana Ilut, Ting Xiao, Michael Chastkofsky, Madina Sukhanova, Nicola Bertolino, Daniele Procissi, Christina Amidei, Craig M. Horbinski, Karen S. Aboody, C. David James, Maciej S. Lesniak, Irina Balyasnikova
Summary: This study demonstrates the efficacy of a bispecific antibody in activating immune cells in patients' tumors and exerting anti-GBM activity. By modifying neural stem cells to produce and secrete the antibody, significant survival benefits were observed in mice with specific types of brain tumors. Further investigation and development of this therapeutic for clinical translation is supported by the results.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Allison M. Bock, Grzegorz S. Nowakowski, Yucai Wang
Summary: Despite challenges in treating R/R NHL, CD20 x CD3 BsAbs have shown promising efficacy with reduced toxicity. With ongoing expansion and registrational studies, approvals for R/R NHL treatment are expected soon. Further exploration is needed to determine the role of BsAbs in treatment-naive NHL and how to combine them with other therapies, as well as to compare and sequence BsAbs with CAR T-cell therapy.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Liping Zhong, Wei Shi, Lu Gan, Xiuli Liu, Yu Huo, Pan Wu, Zhikun Zhang, Tao Wu, Hongmei Peng, Yong Huang, Yongxiang Zhao, Yulin Yuan, Zhiming Deng, Hongliang Tang
Summary: A bispecific T-cell engager antibody targeting human endoglin and CD3 was constructed in this study, showing therapeutic potential in cancer treatment. In vivo experiments demonstrated that the antibody significantly reduced tumor growth and neoangiogenesis, leading to improved mouse survival.
Review
Oncology
Arnold Bolomsky, Meike Vogler, Murat Cem Kose, Caroline A. Heckman, Gregory Ehx, Heinz Ludwig, Jo Caers
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2020)
Correction
Oncology
Arnold Bolomsky, Meike Vogler, Murat Cem Koese, Caroline A. Heckman, Gregory Ehx, Heinz Ludwig, Jo Caers
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marie-Jia Gou, Murat Cem Kose, Jacques Crommen, Cindy Nix, Gael Cobraiville, Jo Caers, Marianne Fillet
Summary: By combining different separation strategies to increase the number of identified proteins in a sample, it can aid in antigen discovery research. Studies have shown that the combination of CZE-DTIMS-QTOF and microfluidic RPLC can provide unique information.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Hematology
Murat Cem Kose, Margaux Lejeune, Marie Jia Gou, Elodie Duray, Gael Cobraiville, Jacques Foguenne, Andre Gothot, Yves Beguin, Mariane Fillet, Jo Caers
Article
Multidisciplinary Sciences
Caroline Ritacco, Murat Cem Kose, Justine Courtois, Lorenzo Canti, Charline Beguin, Sophie Dubois, Benoit Vandenhove, Sophi Servais, Jo Caers, Yves Beguin, Gregory Ehx, Frederic Baron
Summary: Post-transplant administration of cyclophosphamide (PTCy) can attenuate xenogeneic graft-versus-host disease (xGVHD) by depleting proliferative T cells and highly xenoreactive T-cell clones, while not affecting graft-versus-leukemia effects.