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Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC. Here, we developed a humanized and Fc-engineered anti-B7H3 mAb 24F-Hu-mut2 and systematically evaluated its anti-tumor activity in vitro and in vivo. The 24F-Hu-mut2 was humanized and modified in Fc fragment to obtain stronger antibody-dependent cell-mediated cytotoxicity(ADCC) activity and nanomolar affinity. Furthermore, both of ESCC cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice models indicated that 24F-Hu-mut2 displayed potent in vivo anti-tumor activity. In addition, a computational docking model showed that the mAb bound to IgC1 and IgC2 domain of B7-H3, which is closer to the cell membrane. Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo, and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors. [ABSTRACT FROM AUTHOR]

Abstract: The crystal and electronic structures, as well as the luminescence properties of Sr2Al2− x Si1+ x O7− x N x :Eu2+ are reported. First-principles calculations energetically confirm that the Al and Si atoms are in partial ordering in the 2a and 4e sites in Sr2Al2SiO7. In addition, the band structure calculation shows that Sr2Al2SiO7 has an indirect band gap with an energy gap of about 4.07eV, which is in good agreement with the experimental data (∼5.3eV) obtained from the diffuse reflection spectrum. The crystal structure of Sr2Al2SiO7 can be modified by Si–N substitution for Al–O in the lattice with a maximum solubility of about x=0.6. The average bond length of slightly increases although the lattice parameters decrease with the incorporation of Si–N in Sr2Al2SiO7:Eu2+. Under excitation in the visible spectral region, Sr2Al2− x Si1+ x O7− x N x :Eu2+ emits blue to yellow light with a broad emission band in the range of 480–570nm, varying with both the Eu concentration and the x value. The red shift of the emission band of Eu2+ is associated with an increase in the crystal-field splitting and the covalency, which arise from the incorporation of nitrogen as well as the energy transfer between the Eu ions at high Eu concentrations. Moreover, the Eu ions have a strong effect on both the concentration quenching and the thermal quenching in Sr2Al2− x Si1+ x O7− x N x . The temperature dependence of photoluminescence indicates that Sr2Al2− x Si1+ x O7− x N x :Eu2+ shows strong thermal quenching due to the dominant nonradiative process at room temperature. [Copyright &y& Elsevier]