Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.

Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG.
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DOI:
10.1038/s41598-023-31195-6
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发表时间:
2023-03-28
期刊:
影响因子:
4.6
通讯作者:
Cummings, Richard D.
Cummings, Richard D.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matsumoto, Yasuyuki;Jia, Nan;Heimburg-Molinaro, Jamie;Cummings, Richard D.

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The aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors.
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