Article
Biochemistry & Molecular Biology
Juliane Kuklik, Stefan Michelfelder, Felix Schiele, Sebastian Kreuz, Thorsten Lamla, Philipp Mueller, John E. Park
Summary: Insertion of a specific epitope into the VP capsid proteins, combined with bispecific antibody, allows AAV to target new cellular receptors for gene therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Wariya Sanrattana, Thibaud Sefiane, Simone Smits, Nadine D. van Kleef, Marcel H. Fens, Peter J. Lenting, Coen Maas, Steven de Maat
Summary: Serine proteases are crucial for physiological processes and require regulation by serine protease inhibitors. Mutating the reactive center loop can improve serpin function. A platform has been developed to predict the effects of RCL mutagenesis, facilitating the design of therapeutic serpins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Laetitia Misson Mindrebo, Hejun Liu, Gabriel Ozorowski, Quoc Tran, Jordan Woehl, Irene Khalek, Jessica M. Smith, Shawn Barman, Fangzhu Zhao, Celina Keating, Oliver Limbo, Megan Verma, Jingjia Liu, Robyn L. Stanfield, Xueyong Zhu, Hannah L. Turner, Devin Sok, Po-Ssu Huang, Dennis R. Burton, Andrew B. Ward, Ian A. Wilson, Joseph G. Jardine
Summary: Researchers have developed a fully synthetic nanobody library for the treatment of SARS-CoV-2 infection. They generated nanobodies by immunizing camelids and screened and analyzed their structures to find that they can bind to and neutralize SARS-CoV-2. This study provides a blueprint for the development of multispecific molecules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Alan Burke, Florence Borot, Xing Du, Michael Churchill, Jian Ding, Albert Mridul Grass, Philip DeSouza, Abdullah Mahmood Ali, Siddhartha Mukherjee
Summary: This study presents a new method using synthetic orthogonal heterodimers to create a bispecific structure, and demonstrates its effectiveness in leukemia and T-cell mediated cytotoxicity. Additionally, it shows the efficacy of this method in extending survival and reducing leukemia in a mouse model. These results highlight the importance and clinical potential of this approach for bispecific antibodies.
Article
Biochemistry & Molecular Biology
Johanna Voigt, Christoph Meyer, Frank Bordusa
Summary: Bispecific antibodies (bsAbs) are emerging as a leading class of immunotherapies for cancer treatment. This study presents novel chemo-enzymatic and purely enzymatic strategies for generating bispecific antibody fragments, which show promising results in breast cancer cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Review
Chemistry, Multidisciplinary
Adilet Beishenaliev, Yean Leng Loke, Sook Jing Goh, Hui Nee Geo, Malar Mugila, Misni Misran, Lip Yong Chung, Lik Voon Kiew, Steve Roffler, Yin Yin Teo
Summary: Monospecific antibodies have limitations in delivering drugs to tumors with multiple epitopes, while bispecific antibodies provide a promising alternative by simultaneously targeting two distinct antigens or epitopes. This review discusses the roles of bispecific antibodies in enhancing the internalization and intracellular trafficking of drug-conjugated antibodies and facilitating the delivery of drug-encapsulating nanoconstructs.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Biochemistry & Molecular Biology
Cheng Zhang, Nuria Codina, Jiazhi Tang, Haoran Yu, Nesrine Chakroun, Frank Kozielski, Paul A. Dalby
Summary: The research findings highlighted the different destabilizing pathways of protein structure under low pH and high temperature stress conditions, revealing the potential for stabilizing mutations in the CL domain and C-L-C(H)1 interface. The analysis also identified key salt bridge losses as a cause of conformational changes under different stresses, with implications for future engineering efforts to enhance stability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Immunology
Desislava Yanakieva, Lena Vollmer, Andreas Evers, Vanessa Siegmund, Paul Arras, Lukas Pekar, Achim Doerner, Bernhard Valldorf, Harald Kolmar, Stefan Zielonka, Simon Krah
Summary: In this study, a novel symmetric bispecific antibody format was presented by grafting cattle-derived knob paratopes onto peripheral loops of the IgG1 Fc region. Knob architectures obtained from bovine ultralong CDR-H3 antibodies were inserted into the AB loop or EF loop of the CH3 domain to introduce an artificial binding specificity into an IgG molecule. The generated bispecific antibodies demonstrated retained binding affinities of the inserted knob domains and versatile effector cell redirection functionalities without compromising Fc mediated functions such as FcRn or Fc gamma RIIIa binding.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ha Gyeong Shin, Ha Rim Yang, Aerin Yoon, Sukmook Lee
Summary: Harnessing the power of immune cells to combat cancer shows great potential. Through the research of bispecific antibody (bsAb)-based immune-cell engagers (ICEs), effective methods for treating cancer can be discovered and potential therapeutic targets can be identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Biochemical Research Methods
Tianjian Liang, Hui Chen, Jiayi Yuan, Chen Jiang, Yixuan Hao, Yuanqiang Wang, Zhiwei Feng, Xiang-Qun Xie
Summary: The design of therapeutic antibodies has been a focus of attention due to their efficiency and low risk. While experimental methods are time-consuming and expensive, computational techniques have made significant advances. Challenges remain, including antigen flexibility, lack of structural data, and absence of standard design protocols.
BRIEFINGS IN BIOINFORMATICS
(2021)
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.
Article
Multidisciplinary Sciences
Edurne Rujas, Hong Cui, Jonathan Burnie, Clare Burn Aschner, Tiantian Zhao, Sara Insausti, Krithika Muthuraman, Anthony Semesi, Jasper Ophel, Jose L. Nieva, Michael S. Seaman, Christina Guzzo, Bebhinn Treanor, Jean-Philippe Julien
Summary: In this study, HIV-1 bNAbs were engineered by directly fusing their Fab fragments to the human apoferritin light chain, resulting in a multispecific and avid molecule. The molecule exhibited high neutralization potency against a broad panel of HIV-1 pseudoviruses and demonstrated IgG-like bioavailability in vivo through Fc receptor modulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Guanghui Xu, Yuting Luo, Hanbing Wang, Yue Wang, Baorui Liu, Jia Wei
Summary: Bispecific antibodies (BsAbs) have shown promise as immunotherapy strategies, but have been limited to targeting cell surface antigens. However, recent attention has been focused on BsAbs that target intracellular oncoproteins, broadening the scope of tumor antigen targeting and improving the effectiveness of antibody-based therapies.
