Development Of GPC3-targeted Bispecific T Cell Engager For The Treatment Of Hepatocellular Carcinoma And The Anti-tumor Effect Of Anti-EGFRvⅢ Monoclonal Antibody CH12 On Lung Squamous Cell Carcinoma

GPC3(Glypican-3)has been regarded as a potential therapeutic target because of its high frequency expression in hepatocellular carcinoma(HCC)but limited expression in normal tissues.In our study,we developed GPC3-targeted bispecific T cell engager GPC3/CD3 BiTE(which derived from monoclonal antibody 9F2).Then we investigated the antitumor activity of GPC3/CD3 BiTE to treat HCC both in vitro and in vivo.As a result,GPC3/CD3 BiTE could bind to GPC3-positive but not to GPC3-negative HCC cells.Meantime,GPC3/CD3 BiTE could mediate T cells to potential kill GPC3-positive HCC cells in a dose-dependent manner.However,GPC3/CD3 BiTE did not have cytotoxicity on GPC3 negative HCC cells.Finally,GPC3/CD3 BiTE could significantly suppress the growth of Huh-7 and SK-Hep-1 with enforced GPC3 expression cell in vivo.While,treatment in SK-Hep-1 model did not show any antitumor activity in vivo.EGFRvⅢ is the most common variant of Epidermal Growth Factor Receptor(EGFR),which is not expressed on normal tissues.Previous study indicated that EGFRvⅢ was overexpressed on about 16%non-small cell lung cancer(NSCLC)including 5%lung squamous cell carcinoma(LSCC).Thus,EGFRvⅢ might be a potential therapeutic target for LSCC.To find a novel treatment reagent for LSCC,here we explore the possibility of treating LSCC with monoclonal antibody CH12,an anti-EGFRvⅢ monoclonal antibody developed in our lab.Our study demonstrated that CH12 could induce PBMC-dependent cytotoxicity strongly on SK-MES-1-EGFRvⅢ and NCI-H520-EGFRvⅢ cells in vitro,but it had no cytotoxicity against EGFRvⅢ-negative LSCC cells.Additionally,mAb CH12 could completely eliminate the growth of EGFRvⅢ-positive LSCC tumor in vivo.Thus,our study demonstrated that CH12 might be a promising reagent for the treatment of LSCC.