Article
Immunology
Yi Wang, Yuxi Zhang, Haoyi Sun, Jilan Chen, Hui Yang, Zhanqiong Zhong, Xiaoqian Xiao, Yanping Li, Yibei Tang, Haolan Lu, Xinzhi Tang, Mengyang Zhang, Wenjun Wu, Shiyi Zhou, Jiahui Yang
Summary: Over the last decade, immuno-oncologic drugs, particularly CD3-engaging bispecific antibodies (biAbs), have seen rapid development. However, there are still significant challenges in their clinical development for solid tumors, especially non-small cell lung cancer (NSCLC). In this study, a ROR1 x CD3 biAb, called R11 x v9 biAb, was investigated for its tumor-inhibiting role in NSCLC. The biAb demonstrated specific binding to T cells and tumor cells, dose-dependent cytotoxicity against various ROR1+ NSCLC cell lines, and promoted immune responses in tumor tissues. The antitumor activity of R11 x v9 biAb was confirmed in mouse models of ROR1+ NSCLC without observed side effects, supporting further preclinical and clinical studies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Ryan D. D. Molony, Theresa Funk, Gina Trabucco, Erik Corcoran, David Ruddy, Malini Varadarajan, GiNell Elliot, Michelle Piquet, Joni Lam, Matthew J. J. Meyer, Hui Qin Wang, Sema Kurtulus, Haihui Lu
Summary: CD3-engaging bispecific antibodies (BsAbs) enable killing of target cells by forming an immune synapse between T cells and tumor cells, without relying on preexisting tumor specific T cell receptor. It has been found that CD8+ T cells depend on signaling factors derived from CD4+ T cells to achieve sustained killing. The mammalian target of rapamycin (mTOR) pathway and other candidate genes have been identified as intrinsic regulators of BsAb-induced T cell proliferation and/or activation.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Yan Feng, Kun Xie, Yanxin Yin, Bingyu Li, Chenyu Pi, Xiaoqing Xu, Tao Huang, Jingming Zhang, Bo Wang, Hua Gu, Jianmin Fang
Summary: B7-H3 plays a crucial role in tumor progression and is associated with overexpression in various solid tumors, advanced stages, poor clinical outcomes, and resistance to therapy. Researchers have developed a novel anti-B7-H3 x anti-CD3 bispecific antibody that exhibits potent cytotoxic activity against B7-H3-positive tumor cells by improving T cell activation and proliferation. This bispecific antibody also shows strong antitumor activity in animal models.
Article
Immunology
Eline van Diest, Mara J. T. Nicolasen, Lovro Kramer, Jiali Zheng, Patricia Hernandez-Lopez, Dennis X. Beringer, Jurgen Kuball
Summary: In this study, we developed a novel T cell engager concept called GAB by utilizing γδTCR as a tumor targeting domain. The γδ ECTO-alpha CD3-dimer design was found to be superior in function compared to monomers and does not induce T cell activation without simultaneous tumor engagement.
FRONTIERS IN IMMUNOLOGY
(2023)
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
Jie Wang, Chen Li, Kaijie He, Zhihui Kuang, Jia Lu, Ying Yao, Fufan He, Ninghuan Li, Li Li, Fenggen Fu, Zhihai Wu, Shuaixiang Zhou, Dian Kang, Xuan Qiu, Min Wu, Yang Liu, Xiaochao Cao, Mengqiu Xu, Bingliang Chen, Weiwei Wu, Feng Guo
Summary: This study describes a novel therapeutic antibody, IBI38D9-L, for B cell non-Hodgkin lymphomas (B-NHLs). In vitro and in vivo experiments showed that IBI38D9-L selectively kills malignant B cells and activates T cells. The preclinical data indicate that IBI38D9-L has promising efficacy and safety profiles as a potential therapeutic agent for B cell malignancies.
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)
Article
Oncology
Eunhee Lee, Shinai Lee, Sumyeong Park, Yong-Gyu Son, Jiseon Yoo, Youngil Koh, Dong-Yeop Shin, Yangmi Lim, Jonghwa Won
Summary: A novel IgG-based asymmetric bispecific antibody ABL602 2+1, targeting CLL-1 and CD3, showed potent tumor-killing activity and reduced cytokine release, making it a promising candidate for treating patients with AML.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Rui Yang, Susu Shen, Cheng Gong, Xin Wang, Fang Luo, Fengyan Luo, Yang Lei, Zili Wang, Shasha Xu, Qian Ni, Yan Xue, Zhen Fu, Liang Zeng, Lijuan Fang, Yongxiang Yan, Jing Zhang, Lu Gan, Jizu Yi, Pengfei Zhou
Summary: The study demonstrated that the bispecific antibody Y111 efficiently bridged T cells and PD-L1 expressing tumor cells, which enhanced the cytotoxicity of expanded V gamma 2V delta 2 T cells against PD-L1 positive tumor cells. The combination of expanded V gamma 2V delta 2 T cells with Y111 could potentially offer a novel approach for immunotherapy in treating PD-L1 positive solid tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
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)
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
Biochemistry & Molecular Biology
Polina Kaidun, Samuel J. Holzmayer, Sarah M. Greiner, Anna Seller, Christian M. Tegeler, Ilona Hagelstein, Jonas Mauermann, Tobias Engler, Andre Koch, Andreas D. Hartkopf, Helmut R. Salih, Melanie Maerklin
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options. The development of bispecific fusion proteins (BFPs) targeting NKG2DLs has shown promising results in activating NK and T cells against TNBC cells, leading to efficient eradication of tumors. This approach could be a valuable addition to the current treatment options for TNBC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Oncology
Tsung-Yi Lin, Jeong A. Park, Alan Long, Hong-Fen Guo, Nai-Kong Cheung
Summary: The study developed a T cell-engaging bispecific antibody named BC261, which demonstrated potent cytotoxicity against EFT, prostate cancer, and canine osteosarcoma cell lines and showed superior antitumor effects in vivo. BC261 not only promoted T cell infiltration into tumors but also exhibited significant antitumor efficacy against various cancer types.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Kevin Dang, Giulia Castello, Starlynn C. Clarke, Yuping Li, Aarti Balasubramani, Andrew Boudreau, Laura Davison, Katherine E. Harris, Duy Pham, Preethi Sankaran, Harshad S. Ugamraj, Rong Deng, Serena Kwek, Alec Starzinski, Suhasini Iyer, Wim van Schooten, Ute Schellenberger, Wenchao Sun, Nathan D. Trinklein, Roland Buelow, Ben Buelow, Lawrence Fong, Pranjali Dalvi
Summary: TNB-585, an anti-CD3xPSMA TCE, shows promising efficacy in vitro in inducing activation and proliferation of human T cells, killing PSMA(+) prostate tumor cells, and reducing cytokine release and regulatory T cell activation. In addition, TNB-585 demonstrates potent efficacy against patient-derived prostate tumors ex vivo and in vivo, suggesting it may be a promising therapy for mCRPC with lower incidence and severity of CRS compared to TCEs with high-affinity anti-CD3 domains.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)