Article
Biochemistry & Molecular Biology
Dian Xiao, Longlong Luo, Jiaguo Li, Zhihong Wang, Lianqi Liu, Fei Xie, Jiannan Feng, Xinbo Zhou
Summary: The study confirmed for the first time that Atezolizumab is more suitable for designing ADCs compared to Avelumab, with the generated ADC 3 exhibiting potent tumor cell inhibitory activity and immune activation effects. These findings have positive implications for cancer therapy.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Yezhe Cheng, Xiaoxi Yuan, Qiang Tian, Xiuying Huang, Yang Chen, Yuzhi Pu, Hu Long, Mingyu Xu, Yafei Ji, Jia Xie, Yuping Tan, Xi Zhao, Hongmei Song
Summary: The study aimed to enhance the intratumoral accumulation of an antibody-drug conjugate (ADC) and reduce its off-target toxicity. SKB264, a novel ADC targeting trophoblast antigen 2 (TROP2), showed promising pharmacologic profiles in vitro and in vivo, with stronger targeting effect and better antitumor activity compared to IMMU-132. These findings suggest the potential therapeutic efficacy of SKB264 for TROP2-positive tumors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Arnold Lee
Summary: Loncastuximab tesirine is an antibody-drug conjugate developed for the treatment of B cell lymphomas, currently approved in the US for specific types of lymphoma treatment while being researched for treatments of other types of lymphoma.
Review
Medicine, Research & Experimental
Joshuaine Grant, Fei Hua, Joshua F. Apgar, John M. Burke, Diana H. Marcantonio
Summary: The early assessment of dosing requirements is crucial in the development of biotherapeutics. If a high dose is needed for desired efficacy, it may not be feasible or commercially viable to develop the drug unless measures are taken to increase concentration or yield. Understanding the impact of target selection, drug format, and properties on dosing requirements can inform early decisions.
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)
Review
Oncology
Ruipeng Mu, Jiaqi Yuan, Yue Huang, John K. Meissen, Si Mou, Meina Liang, Anton I. Rosenbaum
Summary: In recent years, the development of new modalities in biotherapeutics, such as bioconjugates and novel routes of delivery, has posed challenges for bioanalytical methods. The complexity of bioconjugates makes their quantification crucial for drug discovery and development. Additionally, the potential for in vivo catabolism and biotransformation adds further complexity, requiring thorough investigations in multiple biological matrices. Furthermore, the evaluation and use of excipients to enhance absorption in oral and inhaled biotherapeutics require risk-benefit assessments. Therefore, bioanalytical methods that can measure excipients and potential drug metabolites in biological matrices are highly relevant in addressing these emerging bioanalysis challenges.
Article
Oncology
Min Yuen Teo, Jonathan E. Rosenberg
Summary: Nectin-4 serves as the target for enfortumab vedotin, with its gene expression varying significantly across different molecular subtypes and playing a crucial role in the efficacy of enfortumab vedotin.
CLINICAL CANCER RESEARCH
(2021)
Article
Microbiology
Xia Xiao, Weixuan Lan, Yaqin Zhao, Ruichao Li, Yuan Liu, Juan Liu, Zhiqiang Wang
Summary: PK/PD modeling and Monte Carlo simulations were used to predict the efficacy of florfenicol against Pasteurella multocida strains in ducks. The optimal PK/PD parameter was determined, and a rational dosage regimen was suggested for different strains of P. multocida. Additionally, the PK/PD cutoff values for florfenicol against P. multocida were provided for the current marketed dose and the predicted daily dose in mainland China.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Immunology
Yue Zheng, Yin-Yin Xue, Ya-Qin Zhao, Ye Chen, Zhi-Ping Li
Summary: This case report suggests that despite low HER2 expression in patients with metastatic primary urethral carcinoma, they can still benefit from the combination of Disitamab Vedotin and PD-1 inhibitor, achieving persistent partial remission.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ophelia Yin, Yuan Xiong, Seiko Endo, Kazutaka Yoshihara, Tushar Garimella, Malaz AbuTarif, Russ Wada, Frank LaCreta
Summary: This study characterized the pharmacokinetics of Trastuzumab deruxtecan in patients with HER2-positive breast cancer or other solid tumor malignancies. Results showed no significant differences in steady-state exposure of the drug in different patient populations, suggesting that dose adjustment based on specific patient characteristics is not necessary.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Immunology
Kandasamy Saravanakumar, Sathiyaseelan Anbazhagan, Janandi Pujani Usliyanage, Kumar Vishven Naveen, Udari Wijesinghe, Hu Xiaowen, Veeraraghavan Vishnu Priya, Gobika Thiripuranathar, Myeong-Hyeon Wang
Summary: Nanosized drug carriers, specifically immunonanomedicine, have shown promise in targeting cancer cells. Understanding nanotechnology, cancer biology, immunomedicine, and nanoparticle surface chemistry is crucial for the preparation of effective immuno-nanomedicine. Factors such as nanoparticle type and composition, drug loading, size, shape, and ligand conjugation play important roles in cancer cell targeting and drug release. The selection of specific receptors and their ligand is essential for the development of active immuno-nanomedicines. This review focuses on the fundamental factors and technical challenges in the fabrication of antibody alone or drug conjugated nanoparticles for breast cancer treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Salvatore Siena, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Marwan Fakih, Elena Elez, Javier Rodriguez, Fortunato Ciardiello, Yoshito Komatsu, Taito Esaki, Ki Chung, Zev Wainberg, Andrea Sartore-Bianchi, Kapil Saxena, Eriko Yamamoto, Emarjola Bako, Yasuyuki Okuda, Javad Shahidi, Axel Grothey, Takayuki Yoshino
Summary: This study aimed to investigate the antitumour activity and safety of trastuzurnab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. The drug showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with previous trials. However, careful monitoring and prompt intervention are required for important risks like interstitial lung disease and pneumonitis.
Review
Pharmacology & Pharmacy
Joshua Hurwitz, Lucy Roxana Haggstrom, Elgene Lim
Summary: Antibody-drug conjugates (ADCs) offer new therapeutic options for cancer patients, with the ability to selectively target cancer cells and spare non-malignant tissues. Numerous ADCs are being developed globally, with 13 currently approved. However, limitations such as narrow therapeutic windows, unique toxicity profiles, resistance development, and biomarker selection challenges exist.
Article
Chemistry, Medicinal
Sasha B. Ebrahimi, Xuan Hong, James Ludlow, Dany Doucet, Renuka Thirumangalathu
Summary: Antibody-drug conjugates (ADCs) are highly targeted and potent therapeutics that combine the selectivity of antibodies with the cytotoxicity of drug payloads. However, due to their complex structure and the need for chemical modifications of the payloads, the stability of ADCs can be a challenge. This study utilized high-throughput experimental screens and computational techniques to optimize the conformational and colloidal behavior of a specific ADC, resulting in a more stable structure. The findings provide insights for the development and stabilization of other ADCs.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Hematology
Mehdi Hamadani, John Radford, Carmelo Carlo-Stella, Paolo F. Caimi, Erin Reid, Owen A. O'Connor, Jay M. Feingold, Kirit M. Ardeshna, William Townsend, Melhem Solh, Leonard T. Heffner, David Ungar, Luqiang Wang, Joseph Boni, Karin Havenith, Yajuan Qin, Brad S. Kahl
Summary: Loncastuximab tesirine, an antibody-drug conjugate, shows promising efficacy and safety in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, especially for certain specific lymphoma subtypes. This study suggests that loncastuximab tesirine could be a valuable treatment option for these patients and warrants further investigation in phase 2 trials.
