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
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)
Article
Oncology
Ran You, Jordan Artichoker, Arja Ray, Hugo Gonzalez Velozo, Dan A. Rock, Kip P. Conner, Matthew F. Krummel
Summary: This study characterized the exposure and pharmacodynamic response of an anti-muCD3/anti-huEGFRvIII mouse surrogate BiTE molecule in EGFR variant III-positive breast tumors using intravital imaging. The results revealed heterogeneous temporal and spatial dynamics of BiTE molecule extravasation into solid tumors, indicating physical barriers to its function. High and homogeneous EGFRvIII expression on cancer cells was found to be necessary for efficient tumor clearance by the BiTE molecule. Additionally, the optimal tumor killing required resident tumor-infiltrating lymphocytes (TIL) at high BiTE molecule dosage, while inclusion of peripheral T-cell recruitment was synergistic at moderate to low dosages. Deletion of stimulating conventional type I dendritic cells (cDC1) diminished T-cell activation and tumor clearance induced by the BiTE molecule, suggesting the modulation of in situ antigen-presenting cell (APC) engagements on its efficacy.
CANCER IMMUNOLOGY RESEARCH
(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.
Article
Cell Biology
Zachary R. Crook, Emily J. Girard, Gregory P. Sevilla, Mi-Youn Brusniak, Peter B. Rupert, Della J. Friend, Mesfin M. Gewe, Midori Clarke, Ida Lin, Raymond Ruff, Fiona Pakiam, Tinh-Doan Phi, Ashok Bandaranayake, Colin E. Correnti, Andrew J. Mhyre, Natalie W. Nairn, Roland K. Strong, James M. Olson
Summary: In this study, CDP scaffolds were structurally predicted using I-TASSER and Rosetta protein modeling software, and computationally screened for CDP binders to targets of interest. The resulting high-affinity CDP molecule showed potent T cell killing ability and outperformed a comparator antibody-based molecule in both in vitro and in vivo experiments. This research provides a new approach and tools for the development of CDP therapeutics.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Dingkang Liu, Lichen Bao, Haichao Zhu, Yali Yue, Jing Tian, Xiangdong Gao, Jun Yin
Summary: This study developed a Protease-Activated PSTAGylated BiTE called PAPB, which showed long-acting and highly effective anti-tumor activity in solid tumors. PAPB could release BiTE core to exert its therapeutic effect, and significantly increase T lymphocyte infiltration in tumor tissue. This engineered protein has potential as a promising drug candidate for solid tumor immunotherapy.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Multidisciplinary Sciences
Thanich Sangsuwannukul, Kamonlapat Supimon, Thaweesak Chieochansin, Kornkan Choomee, Jatuporn Sujjitjoon, Mutita Junking, Pa-Thai Yenchitsomanus
Summary: The study demonstrates that T cells secreting alpha CD133-alpha CD3 engager can be an alternative approach to treating CD133-positive CCA, and they exhibit high antitumor activity.
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
Oncology
G. de Jong, L. Bartels, M. Kedde, E. M. E. Verdegaal, M. A. Gillissen, S. E. Levie, M. G. Cercel, S. E. van Hal-van Veen, C. Fatmawati, D. van de Berg, E. Yasuda, Y. B. Claassen, A. Q. Bakker, S. H. van der Burg, R. Schotte, J. Villaudy, H. Spits, M. D. Hazenberg, P. M. van Helden, K. Wagner
Summary: Targeted cancer therapy using monoclonal antibodies has been successful for various types of cancer, but the availability of suitable antibody targets is limited. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, has been identified as a potential therapeutic target against acute myeloid leukemia (AML) and myelodysplastic syndrome. The human antibody AT1413, derived from a high-risk AML patient, has been shown to interact with CD43s and may have therapeutic potential against various types of cancer, including melanoma and breast cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Shiyu Liu, Fan Li, Li Deng, Qiongqiong Ma, Wenyi Lu, Zhuoqian Zhao, Huanzhen Liu, Yixuan Zhou, Manli Hu, Hui Wang, Yingbin Yan, Mingfeng Zhao, Hongkai Zhang, Mingjuan Du
Summary: The combination of bispecific T cell engagers (BiTEs) and oncolytic viruses (OVs) has shown promising results in the treatment of pancreatic cancer, improving the tumor microenvironment, enhancing immune response, and inhibiting tumor growth.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Oncology
Xianglei Liu, Doncho Zhelev, Cynthia Adams, Chuan Chen, John W. Mellors, Dimiter S. Dimitrov
Summary: The fully human antibody B11, with high avidity to CD276, was used to design a more effective B11-BiTE than 8H9-BiTE in targeting 14 different cancer cell lines, showing strong ADCC/ADCP capabilities.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Oncology
Lisa A. King, Elisa C. Toffoli, Myrthe Veth, Victoria Iglesias-Guimarais, Manon C. Slot, Derk Amsen, Rieneke van de Ven, Sarah Derks, Marieke F. Fransen, Jurriaan B. Tuynman, Thilo Riedl, Rob C. Roovers, Anton E. P. Adang, Jurjen M. Ruben, Paul W. H. I. Parren, Tanja D. de Gruijl, Hans J. van der Vliet
Summary: This study assessed the antitumor activity and safety of a bispecific antibody that activates Vy9V82 T cells. In vitro, in vivo, and ex vivo experiments were conducted, and safety was evaluated in nonhuman primates. The findings demonstrated the potential of the antibody to activate Vy9V82 T cells for antitumor activity and its acceptable safety profile, providing a solid basis for further testing in patients with EGFR-positive malignancies.
CANCER IMMUNOLOGY RESEARCH
(2023)
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
Sarah B. Reusing, Dan A. Vallera, Angela R. Manser, Titus Vatrin, Sanil Bhatia, Martin Felices, Jeffrey S. Miller, Markus Uhrberg, Florian Babor
Summary: The text discusses the complexity and rarity of biphenotypic acute lymphoblastic leukemia in children, characterized by CD33 expression. Despite therapies targeting CD19, relapse and resistance remain challenges. Testing the BiKE on NK cells from healthy volunteers and leukemia patients showed enhanced effector functions against CD33(+) cells, suggesting potential as a therapeutic option.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(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)