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Dr. Sumith A. Kularatne Vishal Deshmukh Dr. Marco Gymnopoulos Dr. Sandra L. Biroc Dr. Jinming Xia Shailaja Srinagesh Dr. Ying Sun Dr. Ning Zou Dr. Mark Shimazu Dr. Jason Pinkstaff Dr. Semsi Ensari Nick Knudsen Anthony Manibusan Dr. Jun Y. Axup Dr. Chan Hyuk Kim Prof. Vaughn V. Smider Dr. Tsotne Javahishvili Prof.Dr. Peter G. Schultz 《Angewandte Chemie (International ed. in English)》2013,52(46):12101-12104
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Kim CH Axup JY Dubrovska A Kazane SA Hutchins BA Wold ED Smider VV Schultz PG 《Journal of the American Chemical Society》2012,134(24):9918-9921
Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations. 相似文献
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Dr. Yu Cao Dr. Jun Y. Axup Dr. Jennifer S. Y. Ma Dr. Rongsheng E. Wang Dr. Seihyun Choi Dr. Virginie Tardif Dr. Reyna K. V. Lim Holly M. Pugh Dr. Brian R. Lawson Gus Welzel Dr. Stephanie A. Kazane Dr. Ying Sun Dr. Feng Tian Shailaja Srinagesh Dr. Tsotne Javahishvili Prof. Peter G. Schultz Dr. Chan Hyuk Kim 《Angewandte Chemie (International ed. in English)》2015,54(24):7022-7027
Four different formats of bispecific antibodies (bsAbs) were generated that consist of anti‐Her2 IgG or Fab site‐specifically conjugated to anti‐CD3 Fab using the genetically encoded noncanonical amino acid. These bsAbs varied in valency or in the presence or absence of an Fc domain. Different valencies did not significantly affect antitumor efficacy, whereas the presence of an Fc domain enhanced cytotoxic activity, but triggered antigen‐independent T‐cell activation. We show that the bsAbs can efficiently redirect T cells to kill all Her2 expressing cancer cells, including Her2 1+ cancers, both in vitro and in rodent xenograft models. This work increases our understanding of the structural features that affect bsAb activity, and underscores the potential of bsAbs as a promising therapeutic option for breast cancer patients with low or heterogeneous Her2 expression. 相似文献
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