Early Study On Lgr5/Gpr49 Molecule As A Potential Colon Cancer Stem Cell Target For The Antibody Conjugated Drug Treatment

LGR5 (GPR49) is a Wnt pathway downstream target gene. It has already been confirmed that LGR5 gene is up regulated by APC or β-catenin mutation. LGR5 has recently been identified as a biomarker on the human and murine intestinal or colon stem cells. Our gene expression data shows that LGR5 is highly expressed in colon cancer, with minimal expression in normal tissue. Our strategy in this project is to eliminate tumor stem cells by drug conjugated antibody. Our goal is to find a tumor stem cell marker and develop antibody to target the tumor stem cells. Here we developed and characterized both anti-LGR5 phage and monoclonal antibodies by multi molecular techniques. We finally focus on one phage antibody (YW353) and three monoclonal antibodies (2H6, 3G12 and 8E11) as therapeutic drugs for further study. We evaluated antibody drug conjugate (ADC) in vitro and in vivo with different animal tumor models derived from cell lines and human tumor explants. Good efficacy was observed in these animal models following a single dose of 5mg/kg. Conclusion: LGR5 is an attractive colon cancer target for the administration of anti-LGR5 ADC in human cancer. More in vivo models will be tested to confirm the efficacy and evaluate safety. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4289.