J.Jpn. Surg. Soc.. 123(1): 39-46, 2022

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Feature topic

DEVELOPMENT OF NOVEL CANCER THERAPY USING GLYCAN-LECTIN BINDING

The outermost layer of all cells is covered with a layer of glycans called the glycocalyx. Cell-targeted therapies should be efficient when they target the glycocalyx. However, due to the complexity of glycan structures and limitations of analytical techniques, the specific glycan changes in cancer have not been fully elucidated, and therefore glycan-targeted therapy has not been put into practical clinical use. We conducted comprehensive glycan analysis using lectins, which are glycan-binding proteins, as probes and found that a trisaccharide structure called the H-type 1/3/4 motif is highly expressed in pancreatic cancer. We developed a lectin drug conjugate fusion protein (LDC) that targets pancreatic cancer not with antibodies but with lectins and found it to be extremely potent in vitro with an IC50 of 1.04 pg/ml = 19.5 fmol/L, which is 1000 times stronger than that of conventional immunotoxins (ng/ml order). In addition, it showed remarkable antitumor effects in in vivo subcutaneous tumor models and peritoneal dissemination models and was safe enough to be administered intravascularly without causing any erythrocyte aggregation reaction. Glycan-targeted therapy with lectins could be a new option for targeted anticancer therapy, which has conventionally been dependent on costly antibodies.

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