Double trouble for the tumour glycocode

Subjects

The authors generated GlyTR1 using L-PHA, a tetrameric plant lectin with high specificity for β1,6GlcNAc-branched N-glycans, and GlyTR2 using CD301, a lectin normally found in macrophages and dendritic cells with high specificity for the Tn antigen. Both induced T cell-mediated killing in a target-density dependent manner, independent of major histocompatibility complex expression. Using flow cytometry, both GlyTR1 and GlyTR2 were found to bind to a variety of solid and haematological cancer cell lines. Immunohistochemistry staining of samples from patients with colon adenocarcinoma revealed an increased expression of both TACAs with increasing disease stage.

Owing to a binding mismatch between human CD3 and mouse CD3, the authors next used humanized NOD-scid gamma (NSG) mice to test the in vivo efficacy of both GlyTRs. They both exhibited dose-dependent tumour regression in mice xenografted with triple-negative breast cancer (TNBC), pancreatic adenocarcinoma and ovarian cancer cell lines. Notably, GlyTR exhibited preferential accumulation in the lungs of mice with lung metastatic TNBC, suggesting the potential of GlyTRs for comprehensive disease control.

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