CELL INTELLIGENCE · 肿瘤细胞治疗研究

We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 ( -LGR5). -LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate ( -LGR5-ADC), Bispecific T-cell Engager ( -LGR5-BiTE) and Chimeric Antigen Receptor ( -LGR5-CAR). -LGR5-ADC was the most effective modality for targeting LGR5 + cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment. -LGR5-BiTE treatment was less effective in the pre-B-ALL cancer model yet promoted a twofold reduction in tumour burden. -LGR5-CAR-T cells also showed specific and potent LGR5 + cancer cell killing in vitro and effective tumour targeting with a fourfold decrease in pre-B-ALL tumour burden relative to controls. Taken together, we show that -LGR5 can not only be used as a research tool and a biomarker but also provides a versatile building block for a highly effective immune therapeutic portfolio targeting a range of LGR5-expressing cancer cells.