A novel Tn antigen epitope‑recognizing antibody for MUC1 predicts clinical outcome in patients with primary lung adenocarcinoma

Mucin 1 (MUC1) expression is upregulated in multiple types of cancer, including lung cancer. However, the conventional anti‑MUC1 antibody is not useful for the differentiation of malignant lung tumors and benign lesions due to its limited specificity. Our previous study screened a novel epitope‑defined antibody against cancer‑associated sugar chain structures that specifically recognizes the MUC1 Tn antigen (MUC1‑Tn ED Ab). In the present study, its potential utility as a diagnostic marker and therapeutic tool for lung adenocarcinoma (ADC) was examined. Immunohistochemical analysis of a lung ADC tissue microarray was performed using the MUC1‑Tn ED Ab (clone SN‑102), and the results were compared with those of another clone and commercially available MUC1 antibodies. The association between positive immunoreactivity of SN‑102 and clinicopathologic factors was analyzed. Furthermore, the association between MUC1‑Tn expression and epithelial‑mesenchymal transition markers and radiological characteristics was analyzed. Moderate or high MUC1‑Tn expression (MUC1‑Tn‑H) was observed in 138 (78.9%) of the 175 lung ADC cases. MUC1‑Tn‑H was associated with male sex, cigarette smoking, tumor extension, pleural invasion, and higher preoperative serum carcinoembryonic antigen and cytokeratin 19 fragment levels. Tumors with MUC1‑Tn‑H had higher consolidation/tumor ratios according to computed tomography and greater uptakes of 18F‑fluorodeoxyglucose. A total of 46 (26.9%) of the tumors had mesenchymal features, and MUC1‑Tn positivity was higher in the mesenchymal group than in the epithelial and intermediate groups (P<0.01 and P<0.01, respectively). Patients with tumors exhibiting MUC1‑Tn‑H had significantly shorter 5‑year overall and disease‑free survival times (P=0.011 and P<0.001, respectively). Additionally, MUC1‑Tn‑H was identified as an independent prognostic factor in multivariate analysis (P=0.024). MUC1‑Tn is specific for lung cancer cells and can improve diagnostic capabilities. Additionally, it may be a potential therapeutic target in lung ADC

Rapid Endolysosomal Escape and Controlled Intracellular Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides and Glycopeptides

A novel strategy for the development of a high performance nanoparticules platform was established by means of cell surface mimetic quantum-dots (QDs)-anchored peptides/glycopeptides, which was developed as a model system for nanoparticle-based drug delivery (NDD) vehicles with defined functions helping the specific intracellular trafficking after initial endocytosis. In this paper, we proposed a standardized protocol for the preparation of multifunctional QDs that allows for efficient cellular uptake and rapid escaping from the endolysosomal system and subsequent cytoplasmic molecular delivery to the target cellular compartment. Chemoselective ligation of the ketone-functionalized hexahistidine derivative facilitated both efficient endocytic entry and rapid endolysosomal escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human normal and cancer cells, while modifications of these QDs with cell-penetrating arginine-rich peptides showed poor cellular uptake and induced self-aggregation of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with serglycine-like glycopeptides, namely synthetic proteoglycan initiators (PGIs), elicited the entry and controlled intracellular trafficking, Golgi localization, and also excretion of these nanoparticles, which suggested that the present approach would provide an ideal platform for the design of high performance NDD systems

Correction: A straightforward approach to antibodies recognising cancer specific glycopeptidic neoepitopes (Chem. Sci. (2020) 11 (4999-5006) DOI: 10.1039/D0SC00317D)

Correction for ‘A straightforward approach to antibodies recognising cancer specific glycopeptidic neoepitopes’ by Hajime Wakui et al., Chem. Sci., 2020, 11, 4999–5006, DOI: 10.1039/D0SC00317D