Humanized anti-ganglioside GM2 antibody is effective to induce antibody-dependent cell-mediated cytotoxicity in mononuclear cells from lung cancer patients

Ganglioside GM2 is one of the major gangliosides expressed on the cell surf ace of human tumors including lung cancer. We have previously reported that a mouse-human chimeric monoclonal antibody (mAb), KM966, against GM2 promo tes the lysis of lung cancer cells by human blood mononuclear cells (MNC) o f healthy donors. In this study, we examined antibody-dependent cell-mediat ed cytotoxicity (ADCC) of MNC, using KM966 mAb and its humanized counterpar t, KM8969, in 16 lung cancer patients and 18 control patients. The ADCC act ivity was assessed by 4-h Cr-51 release from GM2 positive SBC-3 small cell lung cancer cells. MNC from lung cancer patients exhibited similar ADCC act ivity to those from control patients when KM966 and KM8969 were used as mAb . Moreover, effective ADCC activity was observed even in MNC from advanced lung cancer patients. These observations suggest the potential activity of humanized anti-GM2 mAb (KM8969), as well as chimeric KM966, in biological t herapy for lung cancer patients. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.