Article
Oncology
Vita Golubovskaya, John Sienkiewicz, Jinying Sun, Yanwei Huang, Liang Hu, Hua Zhou, Hizkia Harto, Shirley Xu, Robert Berahovich, Walter Bodmer, Lijun Wu
Summary: Colorectal cancer, a common cancer worldwide, requires novel treatments. This study developed three different designs of EpCAM-CD3 antibodies and tested their efficacy against colorectal tumors. The antibodies showed high efficacy and specificity, and a novel method of delivering bispecific antibodies using mRNA-LNP technology was demonstrated. The data provide a basis for future clinical studies.
Article
Medicine, Research & Experimental
Yi-nuo Li, Yuan-yuan Li, Shi-xuan Wang, Xiang-yi Ma
Summary: This study aimed to explore the value of M701 in the immunotherapy of ovarian cancer ascites. The expression of EpCAM in ovarian cancer tissues was analyzed, and the effects of M701 on tumor cells and immune cells were examined. The results showed that M701 had a significant killing effect on tumor cells and could induce T cell activation.
CURRENT MEDICAL SCIENCE
(2023)
Article
Oncology
Lijun Wu, Yanwei Huang, John Sienkiewicz, Jinying Sun, Liselle Guiang, Feng Li, Liming Yang, Vita Golubovskaya
Summary: This study investigated novel bispecific antibodies targeting multiple myeloma and found that they demonstrated high efficacy in killing multiple myeloma cells, providing a basis for future clinical studies.
Article
Immunology
Yanlong Liu, Kexin Ao, Fuxiang Bao, Yi Cheng, Yanxia Hao, Huimin Zhang, Shan Fu, Jiaqi Xu, Qiyao Wu
Summary: This study successfully constructed a bispecific single-domain antibody against CD20 and CD3 and demonstrated its function in killing tumor cells. The bispecific antibody specifically bound to CD20 and CD3 molecules and showed significant killing efficiency.
Article
Oncology
Wei-Wei Zheng, Hang Zhou, Ping Li, Shi-Guang Ye, Tuersunayi Abudureheman, Li-Ting Yang, Kai Qing, Ai-Bin Liang, Kai-Ming Chen, Cai-Wen Duan
Summary: CD19 CAR-T cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment, overcoming the escape of CD79b+ CD19- lymphoma cells by redirecting CAR19-T cells to these cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Mary L. Faber, Robyn A. A. Oldham, Archana Thakur, Mary Jo Rademacher, Ewa Kubicka, Theresa A. Dlugi, Steven A. Gifford, William M. Mckillop, Nathan J. Schloemer, Lawrence G. Lum, Jeffrey A. Medin
Summary: CD30 is expressed on various lymphomas and malignancies, making it a potential immunotherapy target. Although anti-CD30 antibody-drug conjugates (ADCs) and chimeric antigen receptors (CARs) have shown promise, alternative treatments are still needed due to their limitations and toxicities. By developing novel anti-CD30 x anti-CD3 bispecific antibodies (biAbs), we aim to coat patient T cells ex vivo with the biAbs and re-infuse them as a safer form of cellular therapy. We have conducted comprehensive studies on the CD30 binding and tumor cell killing properties of these biAbs.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Jim Middelburg, Kristel Kemper, Patrick Engelberts, Aran F. Labrijn, Janine Schuurman, Thorbald van Hall
Summary: CD3-bispecific antibody therapy is a rapidly developing field in immunotherapy, with approved use in hematological malignancies and ongoing research in solid tumors. However, treatment of solid tumors faces more challenges, including increased on-target off-tumor toxicities, sparse T-cell infiltration, and impaired T-cell quality due to an immunosuppressive tumor microenvironment, affecting the safety and efficacy of CD3-bispecific antibody therapy. Various combinatorial approaches are being explored to overcome these hurdles and improve the selectivity and effectiveness of the therapy.
Review
Pharmacology & Pharmacy
Ling Song, Junsheng Xue, Jing Zhang, Si Li, Dongyang Liu, Tianyan Zhou
Summary: This study aimed to predict the in vivo exposure-cytotoxicity relationship and human pharmacokinetics characteristics of bispecific CD3/EpCAM T-cell engager antibody M701 by integrating human PK model into in vivo synapse-based cell killing model. Optimal clinical MABEL dose and PAD for M701 were suggested based on the integrated PK/PD approach.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Stefania C. Carrara, Jan P. Bogen, David Fiebig, Julius Grzeschik, Bjoern Hock, Harald Kolmar
Summary: This study focuses on the role of MerTK receptors in the clearance of apoptotic cells and successfully generates bispecific antibodies that can simultaneously bind EGFR and MerTK. These bispecific antibodies exhibit appropriate binding properties in vitro and promote phagocytosis between macrophages and cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Oncology
Yanping Yang, Jaclyn E. McCloskey, Huan Yang, Janusz Puc, Yago Alcaina, Yogindra Vedvyas, Angel A. Gomez Gallegos, Elizabeth Ortiz-Sanchez, Elisa de Stanchina, Irene M. Min, Eric von Hofe, Moonsoo M. Jin
Summary: The research introduces a bispecific CAR T cell that targets both EpCAM and ICAM-1, achieving more durable antitumor responses regardless of EpCAM expression homogeneity or heterogeneity. Activation of CAR T cells against EpCAM leads to upregulation of ICAM-1, rendering tumors more susceptible to ICAM-1 targeting by bispecific CAR T cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Leila M. Boustany, Sherry L. LaPorte, Laurie Wong, Clayton White, Veena Vinod, Joel Shen, Wendy Yu, David Koditek, Michael B. Winter, Stephen J. Moore, Li Mei, Linnea Diep, Yuanhui Huang, Shouchun Liu, Olga Vasiljeva, Jim West, Jennifer Richardson, Bryan Irving, Marcia Belvin, W. Michael Kavanaugh
Summary: T cell-engaging bispecific antibodies (TCB) are highly potent therapeutics that can recruit and activate cytotoxic T cells to stimulate an antitumor immune response. However, the development of TCBs against solid tumors has been limited by significant on-target toxicity to normal tissues. Probody TCB, targeting EGFR and CD3, has been developed as a novel approach to reduce toxicity to normal tissues and enhance efficacy against solid tumors.
Article
Oncology
Leila M. Boustany, Sherry L. LaPorte, Laurie Wong, Clayton White, Veena Vinod, Joel Shen, Wendy Yu, David Koditek, Michael B. Winter, Stephen J. Moore, Li Mei, Linnea Diep, Yuanhui Huang, Shouchun Liu, Olga Vasiljeva, Jim West, Jennifer Richardson, Bryan Irving, Marcia Belvin, W. Michael Kavanaugh
Summary: This article describes the development of Probody TCB, a novel therapeutic drug that targets EGFR and CD3 and selectively releases its activity in the tumor microenvironment, thereby reducing toxicity to normal tissues. The preclinical studies showed that the drug effectively inhibited tumor growth in vitro and in vivo, while exhibiting lower toxicity in animal models compared to unmasked TCB.
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
Alex A. Shepherd, Bigitha D. Bennychen, Anne Marcil, Darin Bloemberg, Robert Pon, Risini A. Weeratna, Scott A. McComb
Summary: Bi-specific T-cell engager antibodies (BiTEs) are synthetic fusion molecules that induce active contact between T-cells and antigen expressing cells. The current process for BiTE development is time-consuming and costly. This study aims to establish a cost-efficient method for generating and evaluating novel BiTE sequences without purification.
