Publications by authors named "Elisha R Verhaar"
The Class I MHC molecule (MHC-I) HLA-E presents peptides that are derived from the signal sequences, either those of other MHC-I products, or of viral type I membrane glycoproteins. Monoclonal antibodies with proven specificity for HLA-E, and with no cross-reactions with other MHC-I products, have yet to be described. To obtain anti-HLA-E-specific antibodies suitable for a range of applications, we generated monoclonal antibodies against a unique feature of HLA-E: its cytoplasmic tail.
View Article and Find Full Text PDFThe glycoproteins MICA and MICB are upregulated on the surface of cells undergoing stress, for instance due to (viral) infection or malignant transformation. MICA/B are the ligands for the activating receptor NKG2D, found on cytotoxic immune cells like NK cells, CD8 T cells, and γδ T cells. Upon engagement of NKG2D, these cells are activated to eradicate the MICA/B-positive targets, assisted by the secretion of cytokines.
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- MICA and MICB are proteins that increase on cell surfaces during stress from infections or cancer, and they activate immune cells like NK and T cells to destroy these affected cells.
- MICA is often overpresent on cancer cells, especially from epithelial and blood origins.
- Researchers developed stable and easy-to-produce nanobodies that specifically target MICA, which can be fused with a drug to selectively kill tumor cells that express MICA.
Article Synopsis
- Cancer stem cells (CSCs) are key players in tumor recurrence and metastasis, arising from complex epithelial-mesenchymal transitions (EMTs) that create diverse cell states.
- The study successfully isolated pure populations of human breast CSCs using the cell-surface marker integrin β4 (ITGB4) and characterized the underlying gene regulatory network.
- It highlights the role of transcription factors ΔNp63 and p73 in regulating quasi-mesenchymal CSCs, revealing that their activity resembles a regenerative response to injury rather than normal stem cell functions, which promotes cancer spread through autocrine EGFR signaling.
For treatment and diagnosis of cancer, antibodies have proven their value and now serve as a first line of therapy for certain cancers. A unique class of antibody fragments called nanobodies, derived from camelid heavy chain-only antibodies, are gaining increasing acceptance as diagnostic tools and are considered also as building blocks for chimeric antigen receptors as well as for targeted drug delivery. The small size of nanobodies (∼15 kDa), their stability, ease of manufacture and modification for diverse formats, short circulatory half-life, and high tissue penetration, coupled with excellent specificity and affinity, account for their attractiveness.
View Article and Find Full Text PDFCCN2, also known as connective tissue growth factor (CTGF) is a transcriptional target of TGF-β signaling. Unlike its original name ("CTGF") suggested, CCN2 is not an actual growth factor but a matricellular protein that plays an important role in fibrosis, inflammation and connective tissue remodeling in a variety of diseases, including cancer. In pancreatic ductal adenocarcinoma, CCN2 signaling induces stromal infiltration and facilitates a strong tumor-stromal interaction.
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