Therapeutic monoclonal antibodies (mAbs) are successful biomedicines; however, evaluation of their pharmacokinetics and pharmacodynamics demands highly specific discrimination from human immunoglobulin G naturally present in the blood. Here, we developed a novel anti-idiotype aptamer (termed A14#1) with extraordinary specificity against the anti-vascular endothelial growth factor therapeutic mAb, bevacizumab. Structural analysis of the antibody-aptamer complex showed that several bases of A14#1 recognized only the complementarity determining region (CDR) of bevacizumab, thereby contributing to its extraordinary specificity. As the CDR of bevacizumab is predicted to be highly positively charged under mildly acidic conditions and that DNA is negatively charged, the affinity of A14#1 to bevacizumab markedly increased at pH 4.7 (K = 44 pM) than at pH 7.4 (K = 12 nM). A14#1-based electrochemical detection method capable of detecting 31 pM of bevacizumab at pH 4.7 was thus developed. A14#1 could be potentially useful for therapeutic drug measurement as a novel ligand of bevacizumab.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2022.114027DOI Listing

Publication Analysis

Top Keywords

therapeutic monoclonal
8
extraordinary specificity
8
cdr bevacizumab
8
bevacizumab
6
development dna
4
dna aptamer
4
aptamer binds
4
binds complementarity-determining
4
complementarity-determining region
4
therapeutic
4

Similar Publications

Respiratory syncytial virus (RSV) causes high worldwide infant mortality, as well as a high disease burden in the elderly. Efforts in vaccine development over the past 60 years have recently delivered three approved vaccines and two monoclonal antibodies (mAbs). Looking back at the eventful history of RSV vaccine development, several factors can be identified that have hampered the developmental pathway, including the occurrence of enhanced RSV disease (ERD) in the first vaccine attempt and the difficulty in characterizing and stabilizing the pre-fusion F protein as a vaccine target.

View Article and Find Full Text PDF

This study attempted to identify the relevant pathways involved in autophagy activation of pancreatic cancer and explore the mechanisms underlying immune evasion. Western blot (WB) was used to detect the expression of ITGB4, BNIP3, autophagy-related proteins and MHC-I. Co-immunoprecipitation (Co-IP) was used to verify the binding mode of ITGB4 and BNIP3.

View Article and Find Full Text PDF

Introduction: To identify prognostic biomarkers that could predict how well patients will respond to lenvatinib/pembrolizumab (LEN/PEM). The utility of certain inflammatory biomarkers in endometrial liquid-based cytology (LBC) or peripheral blood samples, such as neutrophil counts, lymphocyte counts, and neutrophil-to-lymphocyte ratio (NLR) were explored.

Methods: The study included 25 patients with advanced or recurrent endometrial cancer who had received LEN/PEM between August 2018 and March 2024.

View Article and Find Full Text PDF

Immunotherapy has been advanced through multiple approaches, including immunogenic cytokines, monoclonal antibodies, therapeutic vaccinations, adoptive cell transfer, stem cell transplantation, and oncolytic viruses. This review analyses various strategies in genomics, transcriptomics, single-cell techniques, computational analysis, big data, and imaging technologies for the identification of tumour microbiota and microenvironments. Immunotherapy is becoming acknowledged as a feasible cancer treatment method, facilitating innovative cancer medicines and personalized medicine techniques.

View Article and Find Full Text PDF

Antibodies to watch in 2025.

MAbs

December 2025

Business Intelligence Research, The Antibody Society, Inc., Framingham, MA, USA.

The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!