Novel functional anti-HER3 monoclonal antibodies with potent anti-cancer effects on various human epithelial cancers.

Resistance of progressive cancers against chemotherapy is a serious clinical problem. In this context, human epidermal growth factor receptor 3 (HER3) can play important roles in drug resistance to HER1- and HER2- targeted therapies. Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Novel rat mAbs reacted with HEK293 cells expressing HER3, but not with cells expressing HER1, HER2 or HER4. Specificity of mAbs was substantiated by the loss of mAb binding with knockdown by siRNA and knockout of CRISPR/Cas9-based genome-editing. Analyses of CDR sequence and germline segment have revealed that seven mAbs are classified to four groups, and the binding of patritumab was inhibited by one of seven mAbs. Seven mAbs have shown reactivity with various human epithelial cancer cells, strong internalization activity of cell-surface HER3, and inhibition of NRG1 binding, NRG1-dependent HER3 phosphorylation and cell growth. Anti-HER3 mAbs were also reactive with in vivo tumor tissues and cancer tissue-originated spheroid. Ab4 inhibited in vivo tumor growth of human colon cancer cells in nude mice. Present mAbs may be superior to existing anti-HER3 mAbs and support existing anti-cancer therapeutic mAbs.

Electrosynthesis of Layered Organo-Manganese Dioxide Framework-Doped with Cobalt for Iodide Sensing.

Aqueous Mn2+ ions were anodized at 70 °C with Co2+ in the presence of cationic surfactant, cetyltrimethylammonium (CTA). X-ray diffraction (XRD) analysis revealed that the deposited film possesses a layered structure of MnO2, the interlayer of which is occupied with the assembled CTA molecules. Inclusion of Co ions in the MnO2 film was evidenced by X-ray photoelectron spectroscopy (XPS). They were located in the MnO2 framework, not in the interlayer. The thus-obtained film, CTA-intercalated Co-framework-doped layered MnO2 (CTA/Co-MnO2), was applied as an electrochemical sensor toward iodide (I-), a hydrophobic anion. The organic phase between MnO2 layers could extract I- ions from solution, providing a better sensitivity than a film consisting of layered MnO2 with hydrated alkali metals. On the other hand, the Co-doped layers of MnO2 achieved faster electron transfer kinetics for the oxidation of I-, which resulted in a drastic reduction in response time compared to the nondoped CTA/MnO2.