The combination of programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies has potential for enhancing clinical efficacy. We described the development and antitumor activity of Z15-0, a bispecific nanobody targeting both the PD-1 and CTLA-4 pathways simultaneously. We designed and optimized the mRNA sequence encoding Z15-0, referred to as Z15-0-2 and through a series of in vitro and in vivo experiments, we established that the optimized Z15-0-2 mRNA sequence significantly increased the expression of the bispecific nanobody. Administration of Z15-0-2 mRNA to tumor-bearing mice led to greater inhibition of tumor growth compared to controls. In aggregate, we introduced a novel bispecific nanobody and have re-engineered it to boost expression of mRNA, representing a new drug development paradigm.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245388 | PMC |
| http://dx.doi.org/10.1038/s41388-024-03066-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development and therapeutic assessment of bispecific nanobodies targeting B-cell activating factor and interleukin-17 for the neutralization of inflammatory mediators in autoimmune diseases.
Int J Biol Macromol
January 2025
School of Life Sciences, Zhengzhou University, Henan, Zhengzhou 450001, China; School of Advanced Agricultural Sciences, Peking University, Beijing 100000, China; Longhu Laboratory, Henan, Zhengzhou 450001, China; Henan Key Laboratory of Immunobiology, Henan, Zhengzhou 450001, China; College of Veterinary Medicine, Henan Agricultural University, Henan, Zhengzhou 450001, China. Electronic address:
Autoimmune diseases are characterized by dysregulated immune responses and chronic inflammation. B cell activating factor (BAFF) and interleukin-17 (IL-17) are key mediators in the pathogenesis of several autoimmune diseases, driving B cell hyperactivation, autoantibody production, and tissue damage. Simultaneous targeting of these pathways may provide a synergistic therapeutic approach.
View Article and Find Full Text PDFDrug discovery continues to face a staggering 90% failure rate, with many setbacks occurring during late-stage clinical trials. To address this challenge, there is an increasing focus on developing and evaluating new technologies to enhance the "design" and "test" phases of antibody-based drugs (e.g.
View Article and Find Full Text PDFVisual and High-Efficiency Secretion of SARS-CoV-2 Nanobodies with .
Biomolecules
January 2025
State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan 430062, China.
Nanobodies have gained attention as potential therapeutic and diagnostic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their ability to bind and neutralize the virus. However, rapid, scalable, and robust production of nanobodies for SARS-CoV-2 remains a crucial challenge. In this study, we developed a visual and high-efficiency biomanufacturing method for nanobodies with by fusing the super-folder green fluorescent protein (sfGFP) to the N-terminus or C-terminus of the nanobody.
View Article and Find Full Text PDFTIGIT and PVRIG are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG.
View Article and Find Full Text PDFProteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity.
View Article and Find Full Text PDFWant 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!