Article
Immunology
Chao-Yang Huang, Ying-Yung Lok, Chia-Hui Lin, Szu-Liang Lai, Yen-Yu Wu, Chih-Yung Hu, Chu-Bin Liao, Chen-Hsuan Ho, Yu-Ping Chou, Yi-Hsuan Hsu, Yu-Hsun Lo, Edward Chern
Summary: In this study, a large and highly diverse synthetic human scFv antibody library was constructed, and novel TIM-3-neutralizing antibodies with immunomodulatory functions were identified. These findings demonstrate the potential of this library for biomedical research and the therapeutic potential of the three fully human TIM-3-neutralizing antibodies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hye Lim Choi, Ha Rim Yang, Ha Gyeong Shin, Kyusang Hwang, Ji Woong Kim, Ji Hyun Lee, Taehoon Ryu, Yushin Jung, Sukmook Lee
Summary: Antibody phage display is a crucial technology for discovering and developing target-specific monoclonal antibodies. This study constructed a large human combinatorial single-chain variable fragment library with high diversity, which can be used for the rapid development of recombinant human monoclonal antibodies for therapeutic and diagnostic applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Liujuan Zhou, Fan Yang, Zhaoshuai Bai, Xiaohui Zhou, Zhihai Zhang, Zhihang Li, Junyuan Gong, Junqi Yu, Liqiang Pan, Chan Cao, James J. Chou
Summary: One challenge in improving clinical outcomes of antibody drug conjugates (ADCs) is overcoming cancer resistance to the antibody and/or drug components of ADCs. In this study, a self-assembled left-handed DNA (L-DNA) oligonucleotide was used to link combinatory single-domain antibodies and toxin payloads for tunable and adaptive delivery of ADCs. The newly constructed ADCs with L-DNA scaffold showed promising properties in vitro and in vivo. This suggests that the L-DNA based modular ADC (MADC) platform is a viable option for generating therapeutic ADCs and expanding the therapeutic window.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Virology
Wanzhi Huang, Victoria Soeung, David M. Boragine, Liya Hu, B. V. Venkataram Prasad, Mary K. Estes, Robert L. Atmar, Timothy Palzkill
Summary: This study utilized a high-resolution method to map multiple antibody binding sites simultaneously from complex serum samples. The results indicated that a relatively small number of sites on the virus bind a large number of independently generated antibodies, suggesting that immunodominance plays a role in the humoral immune response to NoV infections.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yu Jung Kim, Min Ho Lee, Se-Ra Lee, Hyo-Young Chung, Kwangmin Kim, Tae Gyu Lee, Dae Young Kim
Summary: Phage display was used to develop human monoclonal antibodies (mAbs) that neutralize SARS-CoV-2. These antibodies showed desirable neutralizing activities and properties, making them potential candidates for antibody therapeutics for treating COVID-19, as well as for diagnostics and research tools.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Menglu Zhao, Chun-Yan Yan, Ya-Nan Wei, Xi-He Zhao
Summary: This review focuses on the mechanisms underlying drug tolerance induced by PD-1/PD-L1 inhibitors and proposes mechanism-based combination therapies and small molecule drugs that target intrinsic immunity and immune checkpoints. Optimization of individualized combination therapy can enhance PD-1/PD-L1-mediated immunoregulation, reduce chemotherapy resistance, and offer new ideas for chemotherapy-resistant cancer.
ANTIVIRAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Courtney P. Jackson, Siteng Fang, Samantha R. Benjamin, Tchilabalo Alayi, Yetrib Hathout, Sarah M. Gillen, Jillian P. Handel, Brittany M. Brems, Justin M. Howe, L. Nathan Tumey
Summary: The use of esters in antibody-drug conjugates (ADCs) has been avoided due to the nature of human esterases. Cellular uptake results in selective but inefficient cleavage of esters by cytosolic esterases. Little cleavage of ester-containing linkers occurs in lysosomes. However, ADCs with ester-linked payloads are active in immune-suppressive assays. The cleavage of ester linkage in plasma depends on the site of attachment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Emily Kang, Cigall Kadoch, James L. Rubenstein, Lewis L. Lanier, James A. Wells
Summary: Through a functional screen, we identified five antibodies that can activate NK cells and enhance their cytotoxicity and interferon-gamma secretion. These antibodies can be further developed into bispecific antibodies to redirect NK cell-mediated cytotoxicity towards CD20+ B cell lymphoma cells and HER2+ breast cancer cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Yaqi Yang, Siji Nian, Lin Li, Xue Wen, Qin Liu, Bo Zhang, Yu Lan, Qing Yuan, Yingchun Ye
Summary: Enhanced EphA2 expression is a crucial target for anti-tumor therapy, with high affinity scFvs against EphA2 successfully screened from an immune library constructed using PBMCs from cancer patients. Modified antibodies showed improved affinity and the ability to bind to EphA2, tumor cells, and tissues, inhibiting tumor growth to some extent. This study highlights the potential of immune libraries from cancer patients in screening for high-affinity antibodies with therapeutic effects.
Review
Immunology
Devesh Aggarwal, Jie Yang, Md. Abdus Salam, Sagnik Sengupta, Md. Yusuf Al-Amin, Saad Mustafa, Mohammad Aasif Khan, Xun Huang, Jogendra Singh Pawar
Summary: Cancer is a deadly disease with non-targeted and toxic conventional therapies. Antibody-drug conjugates (ADCs) offer a precise and effective alternative for cancer treatment. ADCs link a monoclonal antibody to a cytotoxic drug via a chemical linker, targeting cancer cells without harming normal cells. Despite some limitations, ADCs have shown promising results in clinical trials and have been approved for treating various types of cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Frederik Peissert, Louis Pluss, Anna Maria Giudice, Tiziano Ongaro, Alessandra Villa, Abdullah Elsayed, Lisa Nadal, Sheila Dakhel Plaza, Luigi Scietti, Emanuele Puca, Roberto De Luca, Federico Forneris, Dario Neri
Summary: Programmed cell death protein 1 (PD-1) is an immunoregulatory target that can be targeted by different monoclonal antibodies for cancer therapy. In this study, researchers identified a new anti-PD-1 antibody with unique binding specificity and demonstrated its ability to block the interaction between PD-1 and PD-L1.
Article
Biochemistry & Molecular Biology
Chao Xu, Shaojie Liu, Fa Yang, Keying Zhang, Yu Li, Xiaolong Zhao, Jiayu Zhang, Tong Lu, Shiqi Lu, Yao Jiang, Weijun Qin, Changhong Shi, Rui Zhang, An-Gang Yang, Aizhi Zhao, Donghui Han, Weihong Wen
Summary: The study revealed that CD248 can serve as a specific marker for myofibroblasts, and targeting CD248(+) myofibroblasts with an antibody-drug conjugate showed excellent anti-fibrotic effects in mice models.
Article
Biochemistry & Molecular Biology
Benjamin N. Bell, Abigail E. Powell, Carlos Rodriguez, Jennifer R. Cochran, Peter S. Kim
Summary: Infection with SARS-CoV-2 induces robust antibody responses in some patients, with some antibodies effectively inhibiting viral infection by targeting the receptor binding domain (RBD) and blocking interaction with the human receptor ACE2. These antibodies have distinct but overlapping epitopes, demonstrating their effectiveness in neutralizing SARS-CoV-2.
Review
Biochemistry & Molecular Biology
Stephanie Baah, Mark Laws, Khondaker Miraz Rahman
Summary: ADCs are a family of targeted therapeutic agents for cancer treatment, with over 80 currently in clinical development and 11 approved by the FDA. They offer enhanced targeting of cancer cells and reduced toxic side effects compared to traditional approaches, making them an attractive prospect in oncology research.
Article
Pharmacology & Pharmacy
Nick Evans, Ruslan Grygorash, Paul Williams, Andrew Kyle, Terrence Kantner, Ravindra Pathak, XiaoBo Sheng, Fabio Simoes, Hiteshri Makwana, Ricardo Resende, Elena de Juan, Alan Jenkins, David Morris, Aurelie Michelet, Frances Jewitt, Felicity Rudge, Nicolas Camper, Anais Manin, William McDowell, Martin Pabst, Antony Godwin, Mark Frigerio, Matthew Bird
Summary: Antibody-drug conjugates (ADCs) have shown great potential as targeted cancer therapeutics. Recent research has highlighted the importance of linker-payload reagent design in determining the properties of ADCs. This study investigated the impact of incorporating hydrophilic macrocycles into the reagent structures of ADCs, and found that this design can enhance the efficacy of ADCs both in vitro and in vivo.
FRONTIERS IN PHARMACOLOGY
(2022)