Glioblastoma (GB), is the most common and aggressive malignant primary brain tumour in adults. Intra- and inter-tumour heterogeneity, infiltrative GB cell invasion and presence of therapy-resistant GB stem cells (GSCs) represent major obstacles to favourable prognosis and poor therapy response. Identifying the biomarkers of the most aggressive tumour cells and their more efficient targeting strategies are; therefore, crucial. Recently, transcription factor TRIM28 has been identified as a GB biomarker and, in this study, we have shown high expression of TRIM28 in GB and in low grade gliomas as well as higher expression in GSCs vs. differentiated GB cells, although in both cases not significant. We demonstrated significant in vitro inhibition of GB cells and GSCs invasiveness and spread in zebrafish brains in vivo by anti-TRIM28 selective nanobody NB237. TRIM28 was also enriched in GB (tumour) core and associated with the expression of stem cell genes, but was not prognostic for overall survival. However, based on the above results, we conclude that TRIM28 nanobody NB237 offers a new opportunity as a GB therapeutic tool.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434287 | PMC |
| http://dx.doi.org/10.3390/molecules26175141 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lactobacillus reuteri Assists Engineered Bacteria That Target Tumors to Release PD-L1nb to Mitigate the Adverse Effects of Breast Cancer Immunotherapy.
Biotechnol J
December 2024
School of Pharmacy, Binzhou Medical University, Yantai, China.
Programmed death protein-ligand 1 (PD-L1) inhibitors demonstrate significant antitumor efficacy by modulating T-cell activity and inhibiting the PD-1/PD-L1 pathway, thus enhancing immune responses. Despite their robust effects, systemic administration of these inhibitors is linked to severe immune toxicity. To address this issue, we engineered a strain, REP, which releases PD-L1 nanoantibodies (PD-L1nb) to treat breast cancer and attenuate immunotherapy-related side effects.
View Article and Find Full Text PDFExpression-Dependent Tumor Pretargeting via Engineered Avidity.
Mol Pharm
December 2024
Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota 55455, United States.
Selective delivery of therapeutic modalities to tumor cells via binding of tumor-selective cell-surface biomarkers has empowered substantial advances in cancer treatment. Yet, tumor cells generally lack a truly specific biomarker that is present in high density on tumor tissue while being completely absent from healthy tissue. Rather, low but nonzero expression in healthy tissues results in on-target, off-tumor activity with detrimental side effects that constrain the therapeutic window or prevent use altogether.
View Article and Find Full Text PDFαFAP-specific nanobodies mediate a highly precise retargeting of modified AAV2 capsids thereby enabling specific transduction of tumor tissues.
Mol Ther Methods Clin Dev
December 2024
AAV Gene Therapy Research Group, Research Beyond Borders (RBB), Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach an der Riß, Germany.
Due to the refractiveness of tumor tissues to adeno-associated virus (AAV) transduction, AAV vectors are poorly explored for cancer therapy delivery. Here, we aimed to engineer AAVs to target tumors by enabling the specific engagement of fibroblast activation protein (FAP). FAP is a cell surface receptor distinctly upregulated in the reactive tumor stroma, but rarely expressed in healthy tissues.
View Article and Find Full Text PDFENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.
Cell Mol Life Sci
December 2024
Department of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Article Synopsis
- ENPP1/CD203a is an enzyme that breaks down ATP and other nucleotides, influencing purinergic signaling and immune responses.
- The study investigates ENPP1 expression on immune cells using new heavy-chain antibodies and finds high levels in specific cells like CD141 dendritic cells and natural killer cells, while most T cells and B cells show low expression.
- This detailed analysis of ENPP1 expression will aid in understanding its role in immune regulation and could help identify ENPP1-related conditions and tumors for targeted treatments.
NABP-BERT: NANOBODY®-antigen binding prediction based on bidirectional encoder representations from transformers (BERT) architecture.
Brief Bioinform
November 2024
Department of Computer Science and Technology, Xiamen University, Xiamen 361005, China.
Antibody-mediated immunity is crucial in the vertebrate immune system. Nanobodies, also known as VHH or single-domain antibodies (sdAbs), are emerging as promising alternatives to full-length antibodies due to their compact size, precise target selectivity, and stability. However, the limited availability of nanobodies (Nbs) for numerous antigens (Ags) presents a significant obstacle to their widespread application.
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!