Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
In this study we compare the cellular control of recombinant human IgG(4) monoclonal antibody (Mab) synthesis in different CHO cell lines. Based on comprehensive empirical analyses of mRNA and polypeptide synthetic intermediates we constructed cell line-specific mathematical models of recombinant Mab manufacture in seven GS-CHO cell lines varying in specific production rate (qMab) over 350-fold. This comparative analysis revealed that control of qMab involved both genetic construct and cell line-specific factors. With respect to the former, all cell lines exhibited excess production of light chain (LC) mRNA and polypeptide relative to heavy chain (HC) mediated by more rapid LC transcription and enhanced LC mRNA stability. Downstream of this, cell lines differed markedly in their relative rates of recombinant mRNA translation, Mab assembly and secretion although HC mRNA abundance and the rate of HC translation generally exerted most control over qMab--the latter being directly proportional to qMab. This study shows that (i) cell lines capable of high qMab exceed a threshold functional competency in all synthetic processes, (ii) the majority of cells in parental and transfected cell populations are functionally limited and (iii) cell engineering strategies to increase Mab production should be cell line specific.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/bit.22769 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adoptive transfer of third-party donor CMV-specific T cells for refractory cytomegalovirus infection following umbilical cord blood transplantation.
Br J Haematol
September 2025
Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Refractory cytomegalovirus (CMV) infection is a severe complication following umbilical cord blood transplantation (UCBT). Antiviral agents, the standard first-line therapy, are limited by toxicity and resistance without robust T-cell immunity. We evaluated third-party donor (TPD)-derived CMV-specific T cells (CMVSTs) as a treatment option.
View Article and Find Full Text PDFPPM1D is directly degraded by proteasomes in a ubiquitination-independent manner through its carboxyl-terminal region.
J Biomed Sci
September 2025
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Background: PPM1D (protein phosphatase Mg⁺/Mn⁺ dependent 1D) is a Ser/Thr phosphatase that negatively regulates p53 and functions as an oncogenic driver. Its gene amplification and overexpression are frequently observed in various malignancies and disruption of PPM1D degradation has also been reported as a cause of cancer progression. However, the precise mechanisms regulating PPM1D stability remain to be elucidated.
View Article and Find Full Text PDFP2X7 receptor antagonism suppresses epileptiform-like activity in an inflammation-primed human iPSC-derived neuron model of drug-resistant epilepsy.
Br J Pharmacol
September 2025
Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Background And Purpose: Neuroinflammation is increasingly recognised to contribute to drug-resistant epilepsy. Activation of ATP-gated P2X7 receptors has emerged as an important upstream mechanism, and increased P2X7 receptor expression is present in the seizure focus in rodent models and patients. Pharmacological antagonists of P2X7 receptors attenuate seizures in rodents, but this has not been explored in human neural networks.
View Article and Find Full Text PDFA novel FAP-targeting antibody-exatecan conjugate improves immune checkpoint blockade by reversing immunosuppressive microenvironment in pancreatic cancer.
Oncogene
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.
View Article and Find Full Text PDFLEF1 confers resistance to DNA-damaging chemotherapies through upregulation of PARP1 and NUMA1 in ovarian cancer.
Oncogene
September 2025
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Resistance to platinum-based drugs and PARP inhibitors (PARPi) is the leading cause of treatment failure in epithelial ovarian cancer (EOC). This study aimed to identify resistance mechanisms shared by both. Using bioinformatic analyses, EOC tissues, primary tumor cells and organoids, and chemoresistant cell lines, we identified lymphoid enhancer-binding factor 1 (LEF1) as a candidate, whose expression was increased in both platinum-resistant and PARPi-resistant tumors.
View Article and Find Full Text PDF