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
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.
Review
Immunology
Gihoon You, Jonghwa Won, Yangsoon Lee, Dain Moon, Yunji Park, Sang Hoon Lee, Seung-Woo Lee
Summary: BsAbs are emerging as a growing class of immunotherapies with the potential to improve clinical efficacy and safety further. The review describes four classes of BsAbs and presents examples of BsAbs in development. With more data from clinical trials accumulating, BsAbs could be the next generation of new treatment options for cancer patients.
Article
Oncology
Zhaoming Wang, Chaobo Yin, Lawrence G. Lum, Andrean Simons, George J. Weiner
Summary: Research suggests that treatment with anti-CD3 x anti-cancer bispecific antibodies (bsAbs) may enhance T cell help, maintaining long-term NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC).
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Immunology
Jingyue Kang, Tonglin Sun, Yan Zhang
Summary: Bispecific antibodies (bsAbs) are artificial antibodies that can bind to different antigens or different epitopes on the same antigen, thanks to their two distinct antigen-binding sites. They have shown significant potential in tumor treatment and have been extensively researched. Currently, 7 bsAbs have been approved for marketing worldwide, with over 200 bsAbs in various stages of clinical and preclinical research.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
Immunology
Vinicio Melo, Levi Collin Nelemans, Martijn Vlaming, Harm Jan Lourens, Valerie R. Wiersma, Vrouyr Bilemjian, Gerwin Huls, Marco de Bruyn, Edwin Bremer
Summary: A bispecific antibody, CD27xEGFR, has been developed to re-activate T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27. CD27xEGFR binds to both CD27 and EGFR simultaneously, triggering EGFR-restricted co-stimulation of T cells and enhancing T cell cytotoxicity against cancer cells. It has the potential to improve clinical outcomes in various cancers by overcoming the inhibitory factors that suppress T cell activity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Florian Maerkl, Mohamed-Reda Benmebarek, Julius Keyl, Bruno L. Cadilha, Martina Geiger, Clara Karches, Hannah Obeck, Melanie Schwerdtfeger, Stefanos Michaelides, Daria Briukhovetska, Sophia Stock, Jakob Jobst, Philipp Jie Mueller, Lina Majed, Matthias Seifert, Anna-Kristina Kluever, Theo Lorenzini, Ruth Gruenmeier, Moritz Thomas, Adrian Gottschlich, Richard Klaus, Carsten Marr, Michael von Bergwelt-Baildon, Simon Rothenfusser, Mitchell P. Levesque, Markus Vincent Heppt, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: Melanoma is an immune sensitive disease, and immune check point blockade has shown activity. However, TIL therapy after ICB failure has shown promising efficacy, indicating the potential of cellular therapies. To overcome limitations of TIL treatment, a controlled adoptive cell therapy approach using synthetic agonistic receptors and bispecific antibodies targeting melanoma-associated antigens is proposed.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Patricia Himmels, Thi Thu Thao Nguyen, Maresa Caunt Mitzner, Alfonso Arrazate, Stacey Yeung, Jeremy Burton, Robyn Clark, Klara Totpal, Raj Jesudason, Angela Yang, Margaret Solon, Jeffrey Eastham, Zora Modrusan, Joshua D. Webster, Amy A. Lo, Robert Piskol, Weilan Ye
Summary: Preclinical and clinical studies show that T cell-dependent bispecific antibodies (TDBs) not only kill tumors but also cause systemic changes, leading to adverse events. In this study, the acute responses to TDBs in tumor-bearing mice were characterized in detail. The results reveal rapid and significant accumulation of lymphocytes and activation of endothelial cells (ECs) around large blood vessels in normal organs, particularly the liver. It is suggested that differential responses in normal tissues and tumors may be attributed to organ-specific ECs, and a list of genes selectively upregulated in large liver vessels by TDBs is identified. Furthermore, the study demonstrates that CD9 facilitates the interaction between T cells and ECs through the support of ICAM-1 in response to soluble factors released from TDB-mediated cytotoxic reactions. These findings provide insights into the response of different vascular beds to cancer immunotherapy and may contribute to improving their safety and efficacy.
Review
Oncology
Tiancheng Zhang, Youpei Lin, Qiang Gao
Summary: Advances in antibody engineering have led to the development of innovative antibody drugs called bispecific antibodies (bsAbs). These bsAbs have attracted significant interest in cancer immunotherapy by targeting two different antigens and enhancing tumor killing. Cadonilimab (PD-1 x CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, confirming the feasibility of bsAbs in immunotherapy. This review analyzes the mechanisms and emerging applications of bsAbs targeting immunomodulatory checkpoints in cancer immunotherapy.
CANCER BIOLOGY & MEDICINE
(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
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)
Review
Oncology
Yanchen Zhou, Hweixian L. Penny, Mark A. Kroenke, Bianca Bautista, Kelly Hainline, Lynette S. Chea, Jane Parnes, Daniel T. Mytych
Summary: This review discusses the immunogenicity risk assessment of bispecific antibodies (BsAbs) and highlights several risk factors, including novel scaffolds, immunomodulating mechanisms of action, and other product and patient-related factors. The clinical relevance of anti-drug antibodies against BsAbs and advances in tools and strategies for immunogenicity prediction, monitoring, and mitigation are also reviewed. Implementing a drug-specific risk assessment during early development is critical for guiding risk management strategies and improving clinical success.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Tianye Li, Xinrun Wang, Mengke Niu, Mingli Wang, Jianwei Zhou, Kongming Wu, Ming Yi
Summary: The PD-1/PD-L1 signaling pathway is crucial in cancer immune evasion, and anti-PD-1/PD-L1 antibodies are a significant milestone in cancer immunotherapy. However, low response rates and therapeutic resistance remain obstacles. Studies have shown that overexpressed TGF-beta is an additional immunosuppressive factor. Blocking TGF-beta and PD-L1 simultaneously can enhance the efficacy of PD-L1 monoclonal antibodies and overcome resistance. Next-generation bispecific antibodies targeting TGF-beta and PD-L1 have demonstrated superior anti-tumor activity compared to anti-PD-1/PD-L1 monotherapies.
FRONTIERS IN IMMUNOLOGY
(2023)