Lectin Drug Conjugate Therapy for Colorectal Cancer.
2020
Drug resistance represents an obstacle in colorectal cancer treatment because of its association with poor prognoses. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Since fucosylation is often enhanced in many types of cancers, this lectin could be an efficient drug carrier if colorectal cancer cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in colorectal cancer mouse xenograft models. The affinity of rBC2LCN for human colorectal cancer cell lines HT-29, LoVo, LS174T, and DLD-1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN-PE38, was evaluated by MTT-assay. The therapeutic effects and toxicity for each colorectal cancer cell line derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD-1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN-PE38 group was significantly reduced compared with that using control treatment alone. However, the HT-29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds colorectal cancer cells and that rBC2LCN-PE38 significantly suppressed tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each colorectal cancer cell line. These results suggest that lectin drug conjugate therapy has the potential as a novel targeted therapy for colorectal cancer cell surface glycans.
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