Induction of tumor‐cell lysis by bi‐specific antibody recognizing ganglioside GD2 and T‐cell antigen CD3

Human tumor cells expressing ganglioside GD2 were lysed by various effector populations targeted with an anti‐CD3‐anti‐GD2 bi‐specific antibody (BAb CD3 x GD2). This antibodyheteroconjugate was prepared by chemically cross‐linking the OKT‐3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes with the ganglioside MAb ME 361, which binds preferentially to the tumor‐associated ganglioside GD2. The specificity of target‐cell lysis by the cytotoxic T cells (CTL) was mediated by the specificity of the targeting antibody: GD2‐negative cells were not lysed in the presence of the CD3 x GD2 BAb. A dose‐dependent response was observed in a range of 10 to 10,000 ng/ml. In contrast, 2 other BAbs recognizing the tumor‐associated antigens EGF‐R and TKB‐2 had greater potency to mediate tumor‐cell lysis than the GD2 x CD3 BAb. Peripheral‐blood cells (PBL) stimulated with OKT‐3 MAb or with irradiated tumor cells in a mixed lymphocyte culture (MLTC) could be induced to lyse GD2‐positive tumor cells in the presence of CD3 x GD2 BAb. The tumor‐cell lysis could be mediated by autologous or allogeneic effector cells. NK cells had no influence on the BAb‐induced cytotoxicity.