Article
Oncology
Justin T. Huckaby, Elisa Landoni, Timothy M. Jacobs, Barbara Savoldo, Gianpietro Dotti, Samuel K. Lai
Summary: The study demonstrates the in vivo engineering of CAR-T cells using a redirected lentiviral system that offers exceptional specificity and efficiency in controlling the growth of aggressive B cell tumors, highlighting the promising approach for personalized cancer immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(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
Biochemistry & Molecular Biology
Shuyu Huang, Aina Segues, Martin Waterfall, David Wright, Charlotte Vayssiere, Sander M. J. van Duijnhoven, Andrea van Elsas, Alice J. A. M. Sijts, Dietmar M. Zaiss
Summary: T cell engager (TCE) antibodies have shown promise as cancer therapeutics by linking cytotoxic T cells to tumor cells. This study evaluates a novel bispecific antibody format, Fab x sdAb-Fc, as a T-cell redirecting bispecific antibody (TbsAbs) and identifies the hinge design as a key factor influencing their anti-tumor activity.
Article
Radiology, Nuclear Medicine & Medical Imaging
Qian Wang, Jingyun Wang, Hao Yan, Zheng Li, Kun Wang, Feiyu Kang, Jie Tian, Xinming Zhao, Seok-Hyun Yun
Summary: This study aimed to develop an ultra-small-sized, EGFR/VEGF bispecific therapeutic protein to effectively inhibit PDAC tumor growth. The results showed that Bi-fp50 could penetrate deep tumor tissue, inhibit PDAC tumor growth, and potentially serve as a tumor suppressor.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(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
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
Chemistry, Multidisciplinary
Cheng Huang, Xing Duan, Jichao Wang, Qingqing Tian, Yangmei Ren, Kepan Chen, Zongliang Zhang, Yuanyou Li, Yunyu Feng, Kunhong Zhong, Yuelong Wang, Liangxue Zhou, Gang Guo, Xiangrong Song, Aiping Tong
Summary: The study developed a treatment strategy based on mRNA expression, utilizing LNPs to achieve high transfection efficiency and a potent antitumor effect.
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
Oncology
Mirco J. Friedrich, Paola Neri, Niklas Kehl, Julius Michel, Simon Steiger, Michael Kilian, Noemie Leblay, Ranjan Maity, Roman Sankowski, Holly Lee, Elie Barakat, Sungwoo Ahn, Niels Weinhold, Karsten Rippe, Lukas Bunse, Michael Platten, Hartmut Goldschmidt, Carsten Mueller-Tidow, Marc-Steffen Raab, Nizar J. Bahlis
Summary: Bispecific T cell engagers (TCEs) have shown promise in treating various cancers, but the immune mechanisms and molecular determinants of resistance to TCEs are still poorly understood. This study identifies conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy and reveals the association between tumor recognition, exhaustion, and clinical response. The findings also highlight the significance of targeting exhausted-like CD8+ T cells and the loss of target epitope and MHC class I in tumor adaptation to TCEs. These insights advance our understanding of TCE treatment in humans and provide a basis for immune-monitoring and immunotherapy in hematological malignancies.
Article
Oncology
Archana Thakur, Johnson Ung, Elyse N. Tomaszewski, Amy Schienschang, Timothy M. LaBrie, Dana L. Schalk, Lawrence G. Lum
Summary: This study found that bispecific antibody armed activated T cells can target and kill chemo-resistant pancreatic cancer cells and markedly enhance subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters.
Article
Oncology
Martin Hutchings, Franck Morschhauser, Gloria Iacoboni, Carmelo Carlo-Stella, Fritz C. Offner, Anna Sureda, Gilles Salles, Joaquin Martinez-Lopez, Michael Crump, Denise N. Thomas, Peter N. Morcos, Cristiano Ferlini, Ann-Marie E. Broeske, Anton Belousov, Marina Bacac, Natalie Dimier, David J. Carlile, Linda Lundberg, David Perez-Callejo, Pablo Umana, Tom Moore, Martin Weisser, Michael J. Dickinson
Summary: The study evaluated the use of glofitamab in relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) patients. The results showed favorable activity of glofitamab in patients with predominantly refractory, aggressive B-NHL, with frequent and durable complete responses and a predictable and manageable safety profile.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Sung Chang Lee, Jennifer S. Y. Ma, Min Soo Kim, Eduardo Laborda, Sei-Hyun Choi, Eric N. Hampton, Hwayoung Yun, Vanessa Nunez, Michelle T. Muldong, Christina N. Wu, Wenxue Ma, Anna A. Kulidjian, Christopher J. Kane, Vadim Klyushnichenko, Ashley K. Woods, Sean B. Joseph, Mike Petrassi, John Wisler, Jing Li, Christina A. M. Jamieson, Peter G. Schultz, Chan Hyuk Kim, Travis S. Young
Summary: The study introduced a unique semisynthetic bispecific antibody, CCW702, which showed specific and potent in vitro cytotoxicity, good tolerability and subcutaneous bioavailability in mice and cynomolgus monkeys, supporting a weekly dosing regimen testing in patients.
Article
Biochemistry & Molecular Biology
Jie Chen, Zhidi Pan, Lei Han, Yuexian Zhou, Huifang Zong, Lei Wang, Rui Sun, Hua Jiang, Yueqing Xie, Yunsheng Yuan, Mingyuan Wu, Yanling Bian, Baohong Zhang, Jianwei Zhu
Summary: The study constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3, showing high affinity and anti-tumor activity against gastric cancer in vitro and in vivo. It demonstrated stronger T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity compared to the parent monoclonal antibody, indicating potential therapeutic efficacy for gastric cancer.
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
Hematology
Lorenzo Falchi, Santosha A. Vardhana, Gilles A. Salles
Summary: Treatment paradigms for B-cell non-Hodgkin lymphomas (B-NHL) have undergone significant changes in the past two decades due to the introduction of highly active immunotherapies. Bispecific antibodies (BsAb) have emerged as a promising immunotherapeutic for B-NHL, with anti-CD20xCD3 BsAb showing remarkable single-agent activity. However, further research is needed to determine the optimal deployment of these drugs, ideal combination partners, strategies for minimizing toxicity, and pharmacodynamic biomarkers of response and resistance.